Updated on 2025/08/22

写真a

 
ICHIMIYA Shingo
 
Organization
Institute of Immunology Department of Human Immunology Professor
Title
Professor
Homepage
http://web.sapmed.ac.jp/immunology/index.html
External link

Degree

  • MD (1990)、PhD (Medical Science 1994) ( Sapporo Medical University )

Research Interests

  • immune tissues

  • immune cells

  • human immune system

  • immune related disorders

  • follicular helper T cell

  • 疾患モデル動物

Research Areas

  • Life Science / Experimental pathology

  • Life Science / Human pathology

  • Life Science / Immunology

  • Life Science / Laboratory animal science

Education

  • Sapporo Medical University   Graduate School of Medicine

    1990.4 - 1994.3

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    Country： Japan

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  • Sapporo Medical University   School of Medicine

    1984.4 - 1990.3

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    Country： Japan

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Research History

  • Sapporo Medical University   Research Institute for Immunology, Department of Human Immunology   Professor

    2023.10

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  • Sapporo Medical University   School of Medicine   Associate dean

    2022.4

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  • Sapporo Medical University   Research Institute for Frontier Medicine   Director in General

    2021.4 - 2022.3

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  • Sapporo Medical University

    2020.4 - 2022.3

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  • Sapporo Medical University

    2018.4 - 2022.3

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  • Sapporo Medical University   Research Institute for Frontier Medicine, Department of Human Immunology   Professor

    2013.5 - 2023.9

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  • Sapporo Medical University   School of Health Sciences   Professor

    2010.10 - 2013.4

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  • Sapporo Medical University School of Medicine   Department of Pathology   Assistant Professor

    2002.11 - 2010.9

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  • Sapporo Medical University School of Medicine   Department of Pathology   Assistant Professor

    2000.10 - 2002.10

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  • Sapporo Medical University School of Medicine   Department of Surgical Pathology   Assistant Professor

    1998.4 - 2000.9

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  • Chiba Cancer Center   Department of Biochemistry   Research resident

    1996.4 - 1998.3

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  • University of Pennsylvania   Department of Pathology

    1994.4 - 1996.3

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Professional Memberships

Committee Memberships

  • 日本免疫学会   評議員  

    2014   

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    Committee type：Academic society

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  • 日本病理学会   学術評議員  

    2002   

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    Committee type：Academic society

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Papers

  • Unraveling Novel Subsets of Lymphocytes Involved in Sac Expansion in the Tertiary Lymphoid Structure Within an Abdominal Aortic Aneurysm. International journal

    Itaru Hosaka, Ippei Ikegami, Takuma Mikami, Tatsuya Sato, Toshifumi Ogawa, Kei Mukawa, Marenao Tanaka, Keisuke Endo, Yukinori Akiyama, Akihito Ohkawa, Junji Nakazawa, Tsuyoshi Shibata, Tomohiro Nakajima, Yutaka Iba, Chikara Shiiku, Satoshi Sumino, Ryuji Koshima, Kenichi Takano, Shingo Ichimiya, Nobuyoshi Kawaharada, Masato Furuhashi

    Journal of the American Heart Association   e040279   2025.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Chronic inflammation is involved in the development of abdominal aortic aneurysm (AAA). A tertiary lymphoid structure (TLS) within vascular lesions has recently been focused on for its role in modulation of inflammation in local tissues. We aimed to elucidate the relationships between TLS and pathophysiology of AAA. METHODS: Abdominal aortic samples obtained from 37 patients with AAA (men/women: 34/3, age: 72.8±9.9 years) and 15 autopsied patients who died from non-aortic events (men/women: 11/4, age: 65.5±9.8 years) were investigated. RESULTS: TLSs in AAA lesions were confirmed by focal infiltration of CD3-positive cells surrounding germinal center-like structures containing CD20-positive cells between the tunica adventitia and tunica media layers. The formation of a TLS was significantly more prevalent in AAA patients than in autopsied patients. The number of TLSs in AAA lesions was positively correlated with sac diameter (r=0.357, P=0.035) and the amount of intraluminal thrombosis (r=0.466, P=0.005). T cells and B cells were predominant cellular populations among CD45+ cells in AAA lesions. There was a significantly positive correlation between the proportions of interfollicular T follicular helper (CD3+CD4+CD45RA-CXCR5+PD-1+) cells and double negative B (CD3-CD19+IgD-CD27-) cells, and they were positively correlated with sac diameter, intraluminal thrombosis, and serum lipids. Deposited single-cell RNA-sequencing data for AAA showed that T follicular helper cells and double negative B cells were associated with lipid metabolism, T cell activation/proliferation and inflammation. CONCLUSIONS: The formation of a TLS in AAA lesions is associated with sac diameter and intraluminal thrombosis in connection with interfollicular T follicular helper cells and double negative B cells, which may contribute to the pathophysiology of AAA and might be novel therapeutic targets for the development of AAA.

    DOI： 10.1161/JAHA.124.040279

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  • Interleukin 9 mediates T follicular helper cell activation to promote antibody responses

    Taiki Sato, Ippei Ikegami, Masahiro Yanagi, Takeshi Ohyu, Taiki Sugaya, Shotaro Shirato, Masanobu Tanemoto, Shiori Kamiya, Kohei Kikuchi, Yuka Kamada, Takehito Nakata, Ryuta Kamekura, Akinori Sato, Ken-ichi Takano, Masahiro Miyajima, Atsushi Watanabe, Shingo Ichimiya

    Frontiers in Immunology   15   2024.9

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    Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    Antigen-specific humoral responses are orchestrated through complex interactions among immune cells in lymphoid tissues, including the collaboration between B cells and T follicular helper (Tfh) cells. Accumulating evidence indicates a crucial role for interleukin-9 (IL-9) in the formation of germinal centers (GCs), enhancing the generation of class-switched high-affinity antibodies. However, the exact function of IL-9 in Tfh cell regulation remains unclear. In this study, we examined the humoral immune responses of CD4<sup>Cre/+</sup>Il9ra<sup>fl/fl</sup> mice, which lack an IL-9-specific receptor in Tfh cells. Upon intraperitoneal immunization with sheep red blood cells (SRBCs), CD4<sup>Cre/+</sup>Il9ra<sup>fl/fl</sup> mice displayed diminished levels of SRBC-specific IgG antibodies in their sera, along with reduced levels of GC B cells and plasma cells. Notably, Il9ra-deficient Tfh cells in the spleen exhibited decreased expression of their signature molecules such as B-cell lymphoma 6, C-X-C chemokine receptor 5, IL-4, and IL-21 compared to control mice. In models of allergic asthma induced by house dust mite (HDM) inhalation, CD4<sup>Cre/+</sup>Il9ra<sup>fl/fl</sup> mice failed to elevate serum levels of HDM-specific IgE and IgG. This was accompanied by reductions in Tfh cells, GC B cells, and plasma cells in mediastinal lymph nodes. Furthermore, group 2 innate lymphoid cells (ILC2s) were identified as producers of IL-9 under immunizing conditions, possibly induced by leukotrienes released by activated IgD<sup>+</sup> B cells around the T-B border. These observations may indicate the critical role of IL-9 receptor signaling in the activation of Tfh cells, with ILC2s potentially capable of supplying IL-9 in organized lymphoid tissues.

    DOI： 10.3389/fimmu.2024.1441407

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  • Bob1 maintains T follicular helper cells for long-term humoral immunity. International journal

    Masahiro Yanagi, Ippei Ikegami, Ryuta Kamekura, Tatsuya Sato, Taiki Sato, Shiori Kamiya, Kosuke Murayama, Sumito Jitsukawa, Fumie Ito, Akira Yorozu, Miho Kihara, Takaya Abe, Hiromi Takaki, Koji Kawata, Katsunori Shigehara, Satsuki Miyajima, Hirotaka Nishikiori, Akinori Sato, Noritsugu Tohse, Ken-Ichi Takano, Hirofumi Chiba, Shingo Ichimiya

    Communications biology   7 ( 1 )   185 - 185   2024.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    Humoral immunity is vital for host protection, yet aberrant antibody responses can trigger harmful inflammation and immune-related disorders. T follicular helper (Tfh) cells, central to humoral immunity, have garnered significant attention for unraveling immune mechanisms. This study shows the role of B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator, in Tfh cell regulation. Our investigation, utilizing conditional Bob1-deficient mice, suggests that Bob1 plays a critical role in modulating inducible T-cell costimulator expression and cellular respiration in Tfh cells. This regulation maintains the long-term functionality of Tfh cells, enabling their reactivation from central memory T cells to produce antibodies during recall responses. In a bronchial asthma model induced by house dust mite (HDM) inhalation, Bob1 is observed to enhance HDM-specific antibodies, including IgE, highlighting its pivotal function in Tfh cell regulation. Further exploration of Bob1-dependent mechanisms in Tfh cells holds promise for governing protective immunity and addressing immune-related disorders.

    DOI： 10.1038/s42003-024-05827-0

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  • Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases

    Katsunori Shigehara, Ryuta Kamekura, Ippei Ikegami, Hiroshi Sakamoto, Masahiro Yanagi, Shiori Kamiya, Kentaro Kodama, Yuichiro Asai, Satsuki Miyajima, Hirotaka Nishikiori, Eiji Uno, Keisuke Yamamoto, Kenichi Takano, Hirofumi Chiba, Hirofumi Ohnishi, Shingo Ichimiya

    Frontiers in Immunology   14   2023.11

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    Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4<sup>+</sup> cTfh cells were significantly decreased and the percentage of IFN-γ<sup>+</sup> cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.

    DOI： 10.3389/fimmu.2023.1284205

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  • 通年性アレルギー性鼻炎・各種鼻炎:治療・管理・診断 ダニ舌下免疫療法の新しい効果発現のメカニズムの解明

    亀倉 隆太, 重原 克則, 山本 圭佑, 一宮 慎吾, 高野 賢一

    アレルギー   72 ( 6-7 )   872 - 872   2023.8

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    Language：Japanese   Publisher：(一社)日本アレルギー学会  

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  • 原発性肺癌浸潤CD4陽性T細胞組成と浸潤メカニズムの解析

    佐藤 太軌, 石井 大智, 大湯 岳, 千葉 慶宜, 鶴田 航大, 高橋 有毅, 槙 龍之輔, 高瀬 貴章, 宮島 正博, 渡辺 敦, 池上 一平, 一宮 慎吾

    肺癌   63 ( 2 )   130 - 130   2023.4

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    Language：Japanese   Publisher：(NPO)日本肺癌学会  

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  • Immunohistochemical analysis of arachidonate 5-lipoxygenase expression in B-cell lymphomas: Implication for B cell differentiation and its analogy with lymphomagenesis. International journal

    Terufumi Kubo, Tomoki Kikuchi, Masahiko Obata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Shingo Ichimiya, Naoya Nakamura, Toshihiko Torigoe

    Pathology, research and practice   242   154328 - 154328   2023.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    Arachidonate 5-lipoxygenase (ALOX5) is a cardinal enzyme in the synthesis of leukotrienes, which are powerful immune-regulating lipid mediators. We previously reported that ALOX5 is preferentially expressed in B lymphocytes in the mantle zone of human lymphoid tissue. In the context of physiological relevance, the loss of the Alox5 gene in mice significantly impairs the development of follicular B helper T cells and antibody production. However, ALOX5 expression in B-cell lymphomas has not been investigated in detail. In this study, we examined ALOX5 expression in representative B-cell lymphomas and non-neoplastic lymphoid tissues by immunohistochemistry with a commercially available anti-ALOX5 antibody that can be used on formalin-fixed paraffin-embedded specimens. Interestingly, 22/22 cases of mantle cell lymphoma, 7/7 cases of chronic lymphocytic leukemia/small cell lymphoma, and 20/20 cases of follicular lymphoma expressed ALOX5. A small proportion of extranodal marginal zone lymphoma/mucosa-associated lymphoid tissue lymphoma or nodal marginal zone lymphoma cases were positive for ALOX5 (2/13 or 1/3, respectively). In contrast, no cases with diffuse large B-cell lymphoma, regardless of germinal center B cell (GCB) or non-GCB type, expressed ALOX5 (0/25 cases). These findings suggest that ALOX5 may be a novel marker for identifying the cell of origin of B-cell lymphoma. Further investigation is required to clarify the biological significance of ALOX5 expression in lymphoma cells.

    DOI： 10.1016/j.prp.2023.154328

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  • Functional Interplay between IL-9 and Peptide YY Contributes to Chronic Skin Inflammation. International journal

    Shiori Kamiya, Ippei Ikegami, Masahiro Yanagi, Hiromi Takaki, Ryuta Kamekura, Taiki Sato, Keiju Kobayashi, Takafumi Kamiya, Yuka Kamada, Takaya Abe, Ken-Ichi Inoue, Tokimasa Hida, Hisashi Uhara, Shingo Ichimiya

    The Journal of investigative dermatology   142 ( 12 )   3222 - 3231   2022.12

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    Complex interactions between keratinocytes and various cell types, such as inflammatory cells and stromal cells, contribute to the pathogenesis of chronic inflammatory skin lesions. In proinflammatory cytokine‒mediated disease settings, IL-9 plays a pathological role in inflammatory dermatitis. However, IL-9‒related mechanisms remain incompletely understood. In this study, we established tamoxifen-induced keratinocyte-specific IL-9RA-deficient mice (K14CRE/ERTIl9raΔ/Δ mice) to examine the role of IL-9 in multicellular interactions under chronic skin inflammatory conditions. Studies using an imiquimod-induced psoriasis-like model showed that K14CRE/ERTIl9raΔ/Δ mice exhibited a significantly reduced severity of dermatitis and mast cell infiltration compared with control K14WTIl9rafl/fl mice. Transcriptome analyses of psoriasis-like lesions showed that the level of peptide Y-Y (Pyy), a member of the neuropeptide Y family, was markedly downregulated in K14CRE/ERTIl9raΔ/Δ epidermis. Pyy blockade suppressed epidermal thickening and mast cell numbers in imiquimod-treated wild-type mice. Together with in vitro studies indicating that Pyy induced IL-9 production and chemotactic activity in bone marrow‒derived mast cells, these findings suggest that Pyy-mediated interplay between keratinocytes and mast cells contributes to psoriasiform inflammation. Further investigation focusing on the IL-9‒Pyy axis may provide valuable information for the development of new treatment modalities for inflammatory dermatitis.

    DOI： 10.1016/j.jid.2022.06.021

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  • アレルゲン・抗原・免疫療法・検査法 ダニ舌下免疫療法における濾胞Tヘルパー細胞と特異的Igの2年間解析

    重原 克則, 亀倉 隆太, 柳 昌弘, 錦織 博貴, 一宮 慎吾

    アレルギー   71 ( 6-7 )   817 - 817   2022.8

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  • CD4+CD8+ T follicular helper cells regulate humoral immunity in chronic inflammatory lesions. International journal

    Kosuke Murayama, Ippei Ikegami, Ryuta Kamekura, Hiroshi Sakamoto, Masahiro Yanagi, Shiori Kamiya, Taiki Sato, Akinori Sato, Katsunori Shigehara, Motohisa Yamamoto, Hiroki Takahashi, Ken-Ichi Takano, Shingo Ichimiya

    Frontiers in immunology   13   941385 - 941385   2022

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    T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses at the initial and recall phases. Recent studies have indicated the possible involvement of Tfh cells in the process of chronic inflammation. However, the functional role of Tfh cells in persistent immune settings remains unclear. Here, we report that CD4+CD8+ (double-positive, DP; CD3+CD4+CD8+CXCR5hiPD-1hi) Tfh cells, a subset of germinal-center-type Tfh cells, were abundantly present in the fibroinflammatory lesions of patients with immunoglobulin G4-related disease (IgG4-RD). Transcriptome analyses showed that these DP-Tfh cells in the lesions of IgG4-RD preferentially expressed signature genes characteristic of cytotoxic CD8+ T cells, such as Eomes, CRTAM, GPR56, and granzymes, in addition to CD70. Scatter diagram analyses to examine the relationships between tissue-resident lymphocytes and various clinical parameters revealed that the levels of DP-Tfh cells were inversely correlated to the levels of serum IgG4 and local IgG4-expressing (IgG4+) memory B cells (CD19+CD27+IgD-) in patients with IgG4-RD. Cell culture experiments using autologous tonsillar lymphocytes further suggested that DP-Tfh cells possess a poor B-cell helper function and instead regulate memory B cells. Since CD4+ (single positive, SP; CD3+CD4+CD8-CXCR5hiPD-1hi) Tfh cells differentiated into DP-Tfh cells under stimulation with IL-2 and IL-7 as assessed by in vitro experiments, these data imply that SP-Tfh cells are a possible origin of DP-Tfh cells under persistent inflammation. These findings highlight the potential feedback loop mechanism of Tfh cells in immune tolerance under chronic inflammatory conditions. Further studies on DP-Tfh cells may facilitate control of unresolved humoral responses in IgG4-RD pathological inflammation.

    DOI： 10.3389/fimmu.2022.941385

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  • アレルギー性炎症疾患の病態形成における免疫系の役割 細胞傷害性Tph細胞のオリゴクローナルな増殖がIgG4関連疾患の病態形成に関与する

    亀倉 隆太, 村山 公介, 山本 圭佑, 重原 克則, 高野 賢一, 一宮 慎吾

    アレルギー   70 ( 6-7 )   817 - 817   2021.8

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  • 免疫療法 鼻炎合併喘息患者におけるダニ舌下免疫療法の濾胞ヘルパー及び濾胞制御性T細胞を中心とした解析

    重原 克則, 亀倉 隆太, 池上 一平, 柳 昌弘, 山本 圭佑, 一宮 慎吾

    アレルギー   70 ( 6-7 )   789 - 789   2021.8

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  • Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease International journal

    Hayato Yabe, Ryuta Kamekura, Motohisa Yamamoto, Kosuke Murayama, Shiori Kamiya, Ippei Ikegami, Katsunori Shigehara, Hiromi Takaki, Hirofumi Chiba, Hiroki Takahashi, Kenichi Takano, Hiroki Takahashi, Shingo Ichimiya

    Modern Rheumatology   31 ( 1 )   249 - 260   2021.1

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    DOI： 10.1080/14397595.2020.1719576

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  • Cigarette Smoke Underlies the Pathogenesis of Palmoplantar Pustulosis via an IL-17A-Induced Production of IL-36γ in Tonsillar Epithelial Cells. International journal

    Keiju Kobayashi, Ryuta Kamekura, Junji Kato, Shiori Kamiya, Takafumi Kamiya, Kenichi Takano, Shingo Ichimiya, Hisashi Uhara

    The Journal of investigative dermatology   141 ( 6 )   1533 - 1541   2020.11

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    Palmoplantar pustulosis (PPP) is characterized by sterile pustules on the palms and soles. A strong association between PPP and tobacco smoking has been reported, and it has been speculated that the IL-17A pathway may play an important role in PPP. Recent studies have suggested that IL-36 plays a pivotal role in the pathogenesis of psoriasis and its subtypes. The relationships among IL-36, smoking, and PPP have not been examined. Here, we investigated the relationships among the smoking index, severity of the clinical condition of PPP, and in vitro dynamics of IL-36 in human tonsillar epithelial cells under the condition of exposure to a cigarette smoke extract. The results demonstrated that the Palmoplantar Pustulosis Area and Severity Index was strongly and positively correlated with the smoking index in female patients. Immunohistochemical examinations showed that IL-36γ was highly expressed in tonsillar epithelial cells from patients with PPP but not in those from patients with recurrent tonsillitis without PPP. The in vitro study revealed that IL-17A synergistically induced a release of IL-36γ under cigarette smoke extract exposure. These results suggest that local production of IL-36γ by epithelial cells induced by cigarette smoke exposure plays an important role in the pathogenesis of PPP.

    DOI： 10.1016/j.jid.2020.09.028

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  • ダニSLIT中のアレルギー性鼻炎合併喘息における末梢血濾胞ヘルパーT細胞の検討

    重原 克則, 亀倉 隆太, 矢部 隼人, 針生 寛之, 宇野 英二, 一宮 慎吾

    日本呼吸器学会誌   9 ( 増刊 )   324 - 324   2020.8

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  • Activated circulating T follicular helper cells and skewing of T follicular helper 2 cells are down-regulated by treatment including an inhaled corticosteroid in patients with allergic asthma International journal

    Satsuki Miyajima, Katsunori Shigehara, Ryuta Kamekura, Hiromi Takaki, Hayato Yabe, Ippei Ikegami, Yuichiro Asai, Hirotaka Nishikiori, Hirohumi Chiba, Eiji Uno, Hiroki Takahashi, Shingo Ichimiya

    Allergology International   69 ( 1 )   66 - 77   2020.1

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    BACKGROUND: CXCR5+ T follicular helper (TFH) cells primarily promote B cells to produce an antigen-specific antibody through germinal centers (GCs). TFH cells exist in circulation, and circulating(c) TFH2 cells, a subset of cTFH cells, are able to help naïve B cells produce IgE in healthy individuals. Conversely, IL-10-producing regulatory B (Breg) cells inhibit an accelerated immune response. METHODS: We investigated the roles of cTFH cells and cBreg cells based on a TH2 response in patients with atopic asthma (AA). Thirty-two patients with AA and 35 healthy volunteers (HV) were enrolled. We examined cTFH cells including their subsets, their expression of ICOS and PD-1, and cBreg cells by flow cytometry and their associations with clinical biomarkers. Plasma levels of CXCL13, which is a counterpart of CXCR5, were also measured using ELISA. RESULTS: In patients with AA, cTFH2 cells were increased and cTFH1 cells were decreased compared with those in HV. The expression levels of ICOS on cTFH and their subset cells were elevated and Breg cells were greatly decreased. The plasma levels of CXCL13 in patients with AA were significantly elevated and correlated well with the cTFH2/cBreg ratio. These cells were examined in 10 patients AA before and after inhaled corticosteroid (ICS) treatment. Interestingly, the percentages and numbers of TFH2 and ICOS+ cTFH cells declined after ICS treatment together with improvements in symptoms and clinical biomarkers. CONCLUSIONS: The percentages and numbers of cTFH2 and ICOS+ cTFH cells might be useful as biomarkers of TH2 typed airway inflammation in patients with AA.

    DOI： 10.1016/j.alit.2019.08.008

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  • Aberrant populations of circulating T follicular helper cells and regulatory B cells underlying idiopathic pulmonary fibrosis. International journal

    Yuichiro Asai, Hirofumi Chiba, Hirotaka Nishikiori, Ryuta Kamekura, Hayato Yabe, Shun Kondo, Satsuki Miyajima, Katsunori Shigehara, Shingo Ichimiya, Hiroki Takahashi

    Respiratory research   20 ( 1 )   244 - 244   2019.11

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    BACKGROUND: T follicular helper (Tfh) cells have been identified as a new category of helper T cells, which express CXCR5 on their surface and induce the production of antigen-specific antibodies. Many investigations have found morbid proliferation and/or activation of Tfh cells in systemic autoimmune and allergic diseases. It is also known that Tfh cells are regulated by regulatory B (Breg) cells in the deteriorating such diseases. Recently, CXCL13, a ligand of CXCR5, has been reported to increase in the peripheral blood and lungs of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the involvement of Tfh cells and Breg cells in IPF. METHODS: Peripheral blood samples were obtained from 18 patients with IPF. We isolated heparinized peripheral blood mononuclear cells and investigated the proportions of Breg cells, Tfh cells, PD-1+ICOS+ Tfh cells (activated form of Tfh cells), and the Tfh-cell subsets by flow cytometry. These cell profiles were compared with those of 21 healthy controls. Furthermore, we investigated the correlations between profiles of lymphocytes and lung physiology. RESULTS: The median proportions of Tfh cells per total CD4+ T cells and of PD-1+ICOS+ proportion of Tfh cells per total Tfh cells was significantly more in the IPF patients (20.4 and 5.2%, respectively) compared with healthy controls (15.4 and 2.1%, respectively; p = 0.042 and p = 0.004, respectively). The proportion of Tfh2 cells per total Tfh cells was significantly higher and the proportion of Tfh17 was smaller in the IPF patients than healthy controls. The percentage of Breg cells to total B cells was significantly decreased in the IPF patients (median, 8.5%) compared with that in the controls (median, 19.7%; p < 0.001). The proportion of Breg cells was positively correlated with the annual relative change in diffusing capacity of the lungs for carbon monoxide in the IPF patients (r = 0.583, p = 0.018). CONCLUSION: Proliferation and activation of Tfh cells and a decrease in Breg cells were observed in the peripheral blood of patients with IPF. The profile of the Tfh-cell subset also changed. Specific humoral immunity aberration would likely underlie complicated pathophysiology of IPF.

    DOI： 10.1186/s12931-019-1216-6

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  • Interleukin 5-producing ST2+ memory Th2 cells in IgG4-related dacryoadenitis and sialadenitis. Reviewed International journal

    Motohisa Yamamoto, Ken-Ichi Takano, Ryuta Kamekura, Satsuki Aochi, Chisako Suzuki, Shingo Ichimiya, Hiroshi Nakase, Tetsuo Himi, Hiroki Takahashi

    Modern rheumatology   29 ( 5 )   856 - 860   2019.9

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    DOI： 10.1080/14397595.2018.1526357

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  • Bob1 enhances RORγt-mediated IL-17A expression in Th17 cells through interaction with RORγt. Reviewed International journal

    Ikegami I, Takaki H, Kamiya S, Kamekura R, Ichimiya S

    Biochemical and biophysical research communications   514 ( 4 )   1167 - 1171   2019.7

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    DOI： 10.1016/j.bbrc.2019.05.057

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  • 舌下免疫療法 ダニ舌下免疫療法中の喘息合併アレルギー性鼻炎患者における濾胞ヘルパーT細胞を中心とした検討

    重原 克則, 亀倉 隆太, 矢部 勇人, 高木 宏美, 宇野 英二, 一宮 慎吾

    アレルギー   68 ( 4-5 )   503 - 503   2019.5

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  • 生体バリア機構とアレルギー疾患 アレルギー性鼻炎に関連するエピイムノームの新機能

    亀倉 隆太, 矢部 勇人, 重原 克則, 高野 賢一, 一宮 慎吾

    アレルギー   68 ( 4-5 )   320 - 320   2019.5

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  • IL-10<sup>+</sup> T follicular regulatory cells are associated with the pathogenesis of IgG4-related disease. Reviewed International journal

    Ito F, Kamekura R, Yamamoto M, Takano K, Takaki H, Yabe H, Ikegami I, Shigehara K, Himi T, Takahashi H, Ichimiya S

    Immunology letters   207   56 - 63   2019.3

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    DOI： 10.1016/j.imlet.2019.01.008

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  • 鼻炎合併アトピー型喘息患者のダニ抗原SLIT施行における濾胞ヘルパー細胞と濾胞制御性T細胞の検討

    重原 克則, 亀倉 隆太, 矢部 隼人, 宇野 英二, 一宮 慎吾

    日本呼吸器学会誌   8 ( 増刊 )   250 - 250   2019.3

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  • A unique subset of PD-1(+)CXCR5(-)CD4(+) T cells is involved in immunological mechanisms of IgG4-related disease Reviewed

    Kamekura Ryuta, Yamamoto Motohisa, Yabe Hayato, Takaki Hiromi, Takano Kenichi, Takahashi Hiroki, Takahashi Hiroki, Himi Tetsuo, Ichimiya Shingo

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   143 ( 2 )   AB231   2019.2

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  • Retroperitoneal Fibrosis Diagnosed as IgG4-related Disease after 35 Years. Reviewed

    Konno S, Matsuno Y, Ichimiya S, Nishimura M, Kawakami Y

    Internal medicine (Tokyo, Japan)   58 ( 4 )   609 - 613   2019.2

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    DOI： 10.2169/internalmedicine.1241-18

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  • Analysis of allergic reaction in IgG4-related disease. Reviewed International journal

    Yamamoto M, Takano KI, Kamekura R, Aochi S, Suzuki C, Ichimiya S, Takahashi H

    Modern rheumatology   29 ( 6 )   1 - 3   2019.1

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    DOI： 10.1080/14397595.2019.1572488

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  • New insights into IgG4-related disease: emerging new CD4+ T-cell subsets. Reviewed International journal

    Kamekura R, Takahashi H, Ichimiya S

    Current opinion in rheumatology   31 ( 1 )   9 - 15   2019.1

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    DOI： 10.1097/BOR.0000000000000558

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  • Stage classification of IgG4-related dacryoadenitis and sialadenitis by the serum cytokine environment. Reviewed International journal

    Motohisa Yamamoto, Kenichi Takano, Ryuta Kamekura, Chisako Suzuki, Shingo Ichimiya, Tetsuo Himi, Hiroshi Nakase, Hiroki Takahashi

    Modern rheumatology   28 ( 6 )   1004 - 1008   2018.11

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    DOI： 10.1080/14397595.2018.1436029

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  • ダニ舌下免疫療法における血液機能性リンパ球サブセットの経時的変化

    亀倉 隆太, 重原 克則, 伊藤 史恵, 高野 賢一, 氷見 徹夫, 一宮 慎吾

    アレルギー   67 ( 4-5 )   598 - 598   2018.5

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  • アトピー型喘息における治療前後の末梢血濾胞ヘルパーT細胞および制御性B細胞の変化

    重原 克則, 宮島 さつき, 亀倉 隆太, 矢部 隼人, 高橋 弘毅, 一宮 慎吾

    アレルギー   67 ( 4-5 )   637 - 637   2018.5

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  • Revise an educational program in community medical seminars for high-school students in Hokkaido Reviewed

    9 ( 9 )   9 - 14   2018.3

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    Other Link： http://search.jamas.or.jp/link/ui/2018265161

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  • Predicting therapeutic response in IgG4-related disease based on cluster analysis. Reviewed International journal

    Motohisa Yamamoto, Ken-Ichi Takano, Ryuta Kamekura, Chisako Suzuki, Tetsuya Tabeya, Rieko Murakami, Saho Honda, Masaya Mukai, Masanori Nojima, Shingo Ichimiya, Tetsuo Himi, Hiroshi Nakase, Hiroki Takahashi

    Immunological medicine   41 ( 1 )   30 - 33   2018.3

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    To bring the clinical practice of immunoglobulin (Ig)G4-related disease (IgG4-RD) close to personalized medicine, we classified the patient groups and clarified the therapeutic responses of each group. A total of 147 patients enrolled in our registry were classified into four groups by cluster analysis with the software. The therapeutic responses and prognosis of each group were examined. The cluster analysis classified the subjects into four groups: Cluster 1, patients who presented with prominent hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia; Cluster 2, patients who presented with eosinophilia, elevated concentrations of serum IgG, IgG4, and IgE, and in whom CRP tended to be positive; Cluster 3, patients with younger onset and serum levels of IgG, IgG4, and IgE and peripheral eosinophil counts lower than the other clusters; and Cluster 4, patients with elder onset and low peripheral eosinophil counts. The amounts of glucocorticoid for maintenance treatment were from 5 to 7 mg/d in all groups, but the amounts were significantly greater in Cluster 1 (patients with hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia) than in Cluster 4 (elder onset patients, relatively low concentrations of peripheral eosinophils). With regard to the use of immunosuppressants and the relapse rate, there were high frequencies in Cluster 1 and Cluster 3 (younger onset patients who presented with mild elevations of serum IgG and IgG4). On the other hand, Cluster 4 showed a low rate of relapse and often could discontinue steroids. The present results suggest that personalized medicine could be provided in IgG4-RD by classifying patients based on their clinical features.

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  • COPD患者における喘息患者との対比を含めた末梢血濾胞ヘルパーT細胞と制御性B細胞の検討

    重原 克則, 亀倉 隆太, 川田 耕司, 宮島 さつき, 矢部 勇人, 高橋 弘毅, 一宮 慎吾

    日本呼吸器学会誌   7 ( 増刊 )   219 - 219   2018.3

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  • COPD患者における喘息患者との対比を含めた末梢血濾胞ヘルパーT細胞と制御性B細胞の検討

    重原 克則, 亀倉 隆太, 宮島 さつき, 矢部 勇人, 高橋 弘毅, 一宮 慎吾

    日本内科学会雑誌   107 ( Suppl. )   215 - 215   2018.2

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  • Unique profiles of lesional T follicular helper cells in the pathogenesis of IgG4-related disease Reviewed

    Kamekura Ryuta, Yabe Hayato, Takano Kenichi, Yamamoto Motohisa, Ikegami Ippei, Ito Fumie, Takahashi Hiroki, Himi Tetsuo, Ichimiya Shingo

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   141 ( 2 )   AB284   2018.2

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  • Mucosal Immune Response in Nasal-Associated Lymphoid Tissue upon Intranasal Administration by Adjuvants. Reviewed International journal

    Takaki H, Ichimiya S, Matsumoto M, Seya T

    Journal of innate immunity   10 ( 5-6 )   515 - 521   2018

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    DOI： 10.1159/000489405

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  • Circulating PD-1<sup>+</sup>CXCR5<sup>-</sup>CD4<sup>+</sup> T cells underlying the immunological mechanisms of IgG4-related disease. Reviewed International journal

    Kamekura R, Yamamoto M, Takano K, Yabe H, Ito F, Ikegami I, Takaki H, Shigehara K, Suzuki C, Himi T, Takahashi H, Ichimiya S

    Rheumatology advances in practice   2 ( 2 )   rky043   2018

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    OBJECTIVE: The aim was to study the pathological role of lymphocytes with a peripheral T helper-cell-like phenotype (PD-1+CXCR5-CD4+) in IgG4-related disease (IgG4-RD). METHODS: PD-1+CXCR5-CD4+ T cells in the blood of patients with IgG4-RD (n = 53), patients with SS (n = 16) and healthy volunteers (n = 34) as controls were analysed by flow cytometry. Correlations between results obtained by flow cytometry and clinical parameters relevant to IgG4-RD were also analysed. RESULTS: The percentage and absolute number of PD-1+CXCR5- cells within total CD4+ T cells in IgG4-RD patients were significantly increased compared with those in healthy volunteers. Further analysis showed that there were marked positive correlations of the percentage of PD-1+CXCR5-CD4+ T cells with the serum level of IgG4 and the number of organs involved. Interestingly, granzyme A (GZMA)+ cells were enriched in PD-1+CXCR5-CD4+ T cells, and the percentage and absolute number of GZMA+PD-1+CXCR5-CD4+ T cells were significantly elevated in IgG4-RD patients. Although no obvious change was observed in the percentage of total CD4+ T cells, the percentage and absolute number of PD-1+CXCR5-CD4+ T cells decreased in accordance with a reduction of serum IgG4 level after treatment with glucocorticoids. CONCLUSION: In IgG4-RD, circulating CD4+ T-cell populations were composed of PD-1+CXCR5- cells, and the ratios of these cells were correlated with clinical manifestations of IgG4-RD. Further analysis of GZMA+PD-1+CXCR5-CD4+ T cells might lead to a deeper understanding of the pathogenesis of ectopic lymphoid follicles and the persistent inflammation in IgG4-RD.

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  • Keratinocytes in atopic dermatitis express abundant Delta Np73 regulating thymic stromal lymphopoietin production via NF-kappa B Reviewed

    Ayako Kumagai, Terufumi Kubo, Koji Kawata, Ryuta Kamekura, Keiji Yamashita, Sumito Jitsukawa, Tomonori Nagaya, Yasuyuki Sumikawa, Tetsuo Himi, Toshiharu Yamashita, Shingo Ichimiya

    JOURNAL OF DERMATOLOGICAL SCIENCE   88 ( 2 )   175 - 183   2017.11

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    DOI： 10.1016/j.jdermsci.2017.06.017

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  • Loss of sorting nexin 5 stabilizes internalized growth factor receptors to promote thyroid cancer progression Reviewed International journal

    Sumito Jitsukawa, Ryuta Kamekura, Koji Kawata, Fumie Ito, Akinori Sato, Hiroshi Matsumiya, Tomonori Nagaya, Keiji Yamashita, Terufumi Kubo, Tomoki Kikuchi, Noriyuki Sato, Tadashi Hasegawa, Hiroshi Kiyonari, Yoshiko Mukumoto, Ken-ichi Takano, Tetsuo Himi, Shingo Ichimiya

    JOURNAL OF PATHOLOGY   243 ( 3 )   342 - 353   2017.11

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  • High frequency of Bob1(1o) T follicular helper cells in florid reactive follicular hyperplasia Reviewed

    Hiroshi Matsumiya, Koji Kawata, Ryuta Kamekura, Chieko Tsubomatsu, Sumito Jitsukawa, Takamasa Asai, Syunsuke Akasaka, Motonari Kamei, Keiji Yamashita, Fumie Ito, Terufumi Kubo, Noriyuki Sato, Ken-ichi Takano, Tetsuo Himi, Shingo Ichimiya

    IMMUNOLOGY LETTERS   191   23 - 30   2017.11

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    DOI： 10.1016/j.imlet.2017.07.012

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  • Regulation of claudin-4 via p63 in human epithelial cells Reviewed International journal

    Takashi Kojima, Takayuki Kohno, Terufumi Kubo, Yakuto Kaneko, Takuya Kakuki, Akito Kakiuchi, Makoto Kurose, Ken-ichi Takano, Noriko Ogasawara, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Takumi Konno, Shingo Ichimiya, Tetsuo Himi

    ANNALS OF THE NEW YORK ACADEMY OF SCIENCES   1405 ( 1 )   25 - 31   2017.10

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    DOI： 10.1111/nyas.13456

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  • Cutting Edge: A Critical Role of Lesional T Follicular Helper Cells in the Pathogenesis of IgG4-Related Disease Reviewed International journal

    Ryuta Kamekura, Kenichi Takano, Motohisa Yamamoto, Koji Kawata, Katsunori Shigehara, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Akinori Sato, Noriko Ogasawara, Chieko Tsubomatsu, Hiroki Takahashi, Hiroshi Nakase, Tetsuo Himi, Shingo Ichimiya

    JOURNAL OF IMMUNOLOGY   199 ( 8 )   2624 - 2629   2017.10

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    DOI： 10.4049/jimmunol.1601507

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  • Deterioration of regulatory B cells and activation of follicular helper T cells in idiopathic interstitial pneumonias patients Reviewed

    Asai Yuichiro, Chiba Hirofumi, Kondoh Syun, Nishikiori Hirotaka, Takahashi Mamoru, Kuronuma Koji, Otsuka Mitsuo, Yamada Gen, Kamekura Ryuta, Ichimiya Shingo, Takahashi Hiroki

    EUROPEAN RESPIRATORY JOURNAL   50   2017.9

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  • 「自然免疫とアレルギー疾患 最新の病態」に寄せる 腸内細菌による濾胞ヘルパーT細胞制御の可能性と免疫アレルギー病態

    川田 耕司, 一宮 慎吾

    アレルギーの臨床   37 ( 3 )   252 - 255   2017.3

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  • Role of Lesional BCL6hiPD-1hi T Follicular Helper Cells As a Cardinal B-Cell Helper to Produce IgG4 in IgG4-Related Disease Reviewed

    Ryuta Kamekura, Kenichi Takano, Motohisa Yamamoto, Koji Kawata, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Chieko Tsubomatsu, Hiroki Takahashi, Tetsuo Himi, Shingo Ichimiya

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   139 ( 2 )   AB13 - AB13   2017.2

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  • Lipid mediators foster the differentiation of T follicular helper cells Reviewed

    Tomonori Nagaya, Koji Kawata, Ryuta Kamekura, Sumito Jitsukawa, Terufumi Kubo, Motonari Kamei, Noriko Ogasawara, Ken-ichi Takano, Tetsuo Himi, Shingo Ichimiya

    IMMUNOLOGY LETTERS   181   51 - 57   2017.1

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    DOI： 10.1016/j.imlet.2016.11.006

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  • Functional RNAs control T follicular helper cells Reviewed

    Shingo Ichimiya, Ryuta Kamekura, Koji Kawata, Motonari Kamei, Tetsuo Himi

    JOURNAL OF HUMAN GENETICS   62 ( 1 )   81 - 86   2017.1

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  • Importance of "epimmunome" as a new therapeutic target for allergic rhinitis Reviewed

    Ryuta Kamekura, Shingo Ichimiya, Tetsuo Himi

    Japanese Journal of Allergology   66 ( 2 )   91 - 96   2017

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    DOI： 10.15036/arerugi.66.91

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  • Assessing the usefulness of salivary gland biopsy for diagnosis of type-1 autoimmune pancreatitis Reviewed

    Kenichi Takano, Motohisa Yamamoto, Shingo Ichimiya, Hiroki Takahashi, Tetsuo Himi

    MODERN RHEUMATOLOGY   27 ( 3 )   548 - 550   2017

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    DOI： 10.1080/14397595.2016.1209818

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  • KS-2 IgG4関連涙腺・唾液腺炎の病態形成における濾胞ヘルパーT細胞の機能的役割

    亀倉 隆太, 高野 賢一, 山本 元久, 伊藤 史恵, 矢部 勇人, 川田 耕司, 高橋 裕樹, 氷見 徹夫, 一宮 慎吾

    日本臨床免疫学会会誌   40 ( 4 )   292b - 292b   2017

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    <p>【目的】IgG4関連涙腺・唾液腺炎（IgG4-DS）は，涙腺・唾液腺の持続性腫脹と高IgG4血症，局所でのIgG4陽性形質細胞の浸潤を特徴とする疾患である．近年，IgG4産生に関連して，濾胞ヘルパーT（Tfh）細胞と本疾患との関連を示唆する報告が散見されるが，病変部位でのTfh細胞の機能的役割は不明である．【方法】IgG4-DS患者の顎下腺組織からTfh細胞（CD3<sup>+</sup>CD4<sup>+</sup>CXCR5<sup>+</sup>PD-1<sup>hi</sup>）を分離し，DNAマイクロアレイやリアルタイムPCRによる遺伝子発現解析に加え，B細胞との共培養の系でIgG4産生について検討した．比較対照としてヒト口蓋扁桃由来のTfh細胞を用いた．【結果】IgG4-DSの顎下腺組織中に存在するCD4陽性T細胞の多くはCXCR5陽性，PD-1強陽性のTfh細胞であり，口蓋扁桃由来のTfh細胞と比較して，Tfh細胞関連分子（BCL6, CXCL13, IL-10）の発現上昇を認めた．また，IgG4-DSの顎下腺由来Tfh細胞とB細胞との共培養で，口蓋扁桃由来のTfh細胞とB細胞との共培養と比較して，より効率的にIgG4の産生が誘導された．さらにDNAマイクロアレイによる解析でIgG4-DSの顎下腺由来のTfh細胞ではCD8A, Granzyme Kといった細胞障害性T細胞関連遺伝子の発現上昇を認めた．【結論】今回の結果から，IgG4-DSの病態形成に強力な抗体産生誘導能と細胞障害能を併せ持つ特殊なTfh細胞が関与している可能性が考えられた．病変部位におけるTfh細胞が，IgG4-DSの新規治療法を開発する上での治療標的となる可能性が示唆された．</p>

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  • Bob1 limits cellular frequency of T-follicular helper cells (vol 46, pg 1361, 2016) Reviewed

    Keiji Yamashita, Koji Kawata, Hiroshi Matsumiya, Ryuta Kamekura, Sumito Jitsukawa, Tomonori Nagaya, Noriko Ogasawara, Ken-ichi Takano, Terufumi Kubo, Sachiko Kimura, Katsunori Shigehara, Tetsuo Himi, Shingo Ichimiya

    EUROPEAN JOURNAL OF IMMUNOLOGY   46 ( 8 )   2054 - 2054   2016.8

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  • Clinicopathological analysis of salivary gland tissue from patients with IgG4-related disease Reviewed

    Kenichi Takano, Kazuaki Nomura, Ayumi Abe, Ryuta Kamekura, Motohisa Yamamoto, Shingo Ichimiya, Hiroki Takahashi, Tetsuo Himi

    ACTA OTO-LARYNGOLOGICA   136 ( 7 )   717 - 721   2016.7

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    DOI： 10.3109/00016489.2016.1154605

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  • Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation Reviewed

    Akinori Sato, Ryuta Kamekura, Koji Kawata, Masaya Kawada, Sumito Jitsukawa, Keiji Yamashita, Noriyuki Sato, Tetsuo Himi, Shingo Ichimiya

    PLOS ONE   11 ( 7 )   e0158408   2016.7

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  • Identification of a novel human memory T-cell population with the characteristics of stem-like chemo-resistance Reviewed

    Kenji Murata, Tomohide Tsukahara, Makoto Emori, Yuji Shibayama, Emi Mizushima, Hiroshi Matsumiya, Keiji Yamashita, Mitsunori Kaya, Yoshihiko Hirohashi, Takayuki Kanaseki, Terufumi Kubo, Tetsuo Himi, Shingo Ichimiya, Toshihiko Yamashita, Noriyuki Sato, Toshihiko Torigoe

    OncoImmunology   5 ( 6 )   e1165376   2016.6

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  • Bob1 limits cellular frequency of T-follicular helper cells Reviewed

    Keiji Yamashita, Koji Kawata, Hiroshi Matsumiya, Ryuta Kamekura, Sumito Jitsukawa, Tomonori Nagaya, Noriko Ogasawara, Ken-ichi Takano, Terufumi Kubo, Sachiko Kimura, Katsunori Shigehara, Tetsuo Himi, Shingo Ichimiya

    EUROPEAN JOURNAL OF IMMUNOLOGY   46 ( 6 )   1361 - 1370   2016.6

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  • Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells Reviewed

    Akari Hashimoto, Tsutomu Sato, Satoshi Iyama, Masahiro Yoshida, Soushi Ibata, Ayumi Tatekoshi, Yusuke Kamihara, Hiroto Horiguchi, Kazuyuki Murase, Yutaka Kawano, Kohichi Takada, Koji Miyanishi, Masayoshi Kobune, Shingo Ichimiya, Junji Kato

    PLOS ONE   11 ( 3 )   e0152823   2016.3

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  • Role of Circulating ICOS plus Follicular Helper T Cells in the Pathogenesis of Birch Pollen Allergy Reviewed

    Ryuta Kamekura, Koji Kawata, Sumito Jitsukawa, Tomonori Nagaya, Keiji Yamashita, Fumie Ito, Kenichi Takano, Katsunori Shigehara, Tetsuo Himi, Shingo Ichimiya

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   137 ( 2 )   AB393 - AB393   2016.2

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  • Role of crosstalk between epithelial and immune cells, the epimmunome, in allergic rhinitis pathogenesis Reviewed

    Ryuta Kamekura, Keiji Yamashita, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Shingo Ichimiya, Tetsuo Himi

    Advances in Oto-Rhino-Laryngology   77   75 - 82   2016

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  • Identification of a novel human memory T-cell population with the characteristics of stem-like chemo-resistance Reviewed

    Kenji Murata, Tomohide Tsukahara, Makoto Emori, Yuji Shibayama, Emi Mizushima, Hiroshi Matsumiya, Keiji Yamashita, Mitsunori Kaya, Yoshihiko Hirohashi, Takayuki Kanaseki, Terufumi Kubo, Tetsuo Himi, Shingo Ichimiya, Toshihiko Yamashita, Noriyuki Sato, Toshihiko Torigoe

    ONCOIMMUNOLOGY   5 ( 6 )   2016

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  • Studies of tonsils in basic and clinical perspectives: From the past to the future Reviewed

    Keiji Yamashita, Shingo Ichimiya, Ryuta Kamekura, Tomonori Nagaya, Sumito Jitsukawa, Hiroshi Matsumiya, Kenichi Takano, Tetsuo Himi

    Advances in Oto-Rhino-Laryngology   77   119 - 124   2016

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  • Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma Reviewed

    Ryuta Karnekura, Katsunori Shigehara, Satsuki Miyajima, Sumito Jitsukawa, Koji Kawata, Keiji Yamashita, Tomonori Nagaya, Ayako Kumagai, Akinori Sato, Hiroshi Matsumiya, Noriko Ogasawara, Nobuhiko Seki, Kenichi Takano, Yasuo Kokai, Hiroki Takahashi, Tetsuo Himi, Shingo Ichimiya

    CLINICAL IMMUNOLOGY   158 ( 2 )   204 - 211   2015.6

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  • Alteration of human blood type 2 follicular helper T cells and regulatory B cells underlies comorbid association of allergic rhinitis with bronchial asthma Reviewed

    Ryuta Kamekura, Katsunori Shigehara, Sumito Jitsukawa, Koji Kawata, Tetsuo Himi, Shingo Ichimiya

    JOURNAL OF IMMUNOLOGY   194   2015.5

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  • アレルギー性気道疾患の病態形成における濾胞ヘルパーT細胞と制御性B細胞の役割

    亀倉 隆太, 重原 克則, 實川 純人, 小笠原 徳子, 高野 賢一, 氷見 徹夫, 一宮 慎吾

    アレルギー   64 ( 3-4 )   570 - 570   2015.4

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  • アトピー型気管支喘息における末梢血濾胞ヘルパーT細胞の解析

    重原 克則, 亀倉 隆太, 宮島 さつき, 高橋 弘毅, 伊藤 進, 一宮 慎吾

    日本呼吸器学会誌   4 ( 増刊 )   244 - 244   2015.3

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  • 扁桃・アデノイドはなぜあるのか?鼻はなにをしているのか? 粘膜免疫・粘膜防御の最前線を探る

    氷見 徹夫, 高野 賢一, 山下 恵司, 小笠原 徳子, 山本 圭佑, 堤 裕幸, 小島 隆, 一宮 慎吾, 澤田 典均, 横田 伸一

    顎顔面口腔育成会誌   3 ( 1 )   3 - 6   2015.3

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  • Tight junction protein claudin-4 is modulated via Delta Np63 in human keratinocytes Reviewed

    Terufumi Kubo, Kotaro Sugimoto, Takashi Kojima, Norimasa Sawada, Noriyuki Sato, Shingo Ichimiya

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   455 ( 3-4 )   205 - 211   2014.12

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  • Specific Targeting of a Naturally Presented Osteosarcoma Antigen, Papillomavirus Binding Factor Peptide, Using an Artificial Monoclonal Antibody Reviewed

    Tomohide Tsukahara, Makoto Emori, Kenji Murata, Takahisa Hirano, Norihiro Muroi, Masanori Kyono, Shingo Toji, Kazue Watanabe, Toshihiko Torigoe, Vitaly Kochin, Hiroko Asanuma, Hiroshi Matsumiya, Keiji Yamashita, Tetsuo Himi, Shingo Ichimiya, Takuro Wada, Toshihiko Yamashita, Tadashi Hasegawa, Noriyuki Sato

    JOURNAL OF BIOLOGICAL CHEMISTRY   289 ( 32 )   22035 - 22047   2014.8

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  • Delta Np63 Controls a TLR3-Mediated Mechanism That Abundantly Provides Thymic Stromal Lymphopoietin in Atopic Dermatitis Reviewed

    Terufumi Kubo, Ryuta Kamekura, Ayako Kumagai, Koji Kawata, Keiji Yamashita, Yukari Mitsuhashi, Takashi Kojima, Kotaro Sugimoto, Akihiro Yoneta, Yasuyuki Sumikawa, Toshiharu Yamashita, Noriyuki Sato, Tetsuo Himi, Shingo Ichimiya

    PLOS ONE   9 ( 8 )   e105498   2014.8

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  • Multifocal and microscopic chromophobe renal cell carcinomatous lesions associated with 'capsulomas' without FCLN gene abnormality Reviewed

    Kotaro Sugimoto, Akira Takasawa, Shingo Ichimiya, Masaki Murata, Hiromichi Kimura, Tomoyuki Aoyama, Johan J.P. Gille, Naoto Kuroda, Hiroshi Shimizu, Tadashi Hasegawa, Norimasa Sawada, Mitsuko Furuya, Yoji Nagashima

    Pathology International   63 ( 10 )   510 - 515   2013.10

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  • アトピー型気管支喘息患者における血清IL-9の検討

    重原 克則, 伊藤 進, 一宮 慎吾

    日本呼吸器学会誌   2 ( 増刊 )   156 - 156   2013.3

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  • Sorting nexin 5 of a new diagnostic marker of papillary thyroid carcinoma regulates Caspase-2 Reviewed

    Shihoko Ara, Tomoki Kikuchi, Hiroshi Matsumiya, Takashi Kojima, Terufumi Kubo, Rui Carrie Ye, Akinori Sato, Shin-ichiro Kon, Tomo Honma, Kohji Asakura, Tadashi Hasegawa, Tetsuo Himi, Noriyuki Sato, Shingo Ichimiya

    CANCER SCIENCE   103 ( 7 )   1356 - 1362   2012.7

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  • POU2AF1(+) follicular helper T (Tfh) cells in obstructive sleep apnea syndrome (OSAS) Reviewed

    Shingo Ichimiya, Hiroshi Matsumiya, Terufumi Kubo, Shihoko Ara, Rui Ye, Akinori Sato, Tomoki Kikuchi, Keiji Yamashita, Yukari Mitsuhashi, Nobuhiko Seki, Hideaki Shirasaki, Sachiko Kimura, Shigeaki Yokoyama, Noriyuki Sato, Tetsuo Himi

    JOURNAL OF IMMUNOLOGY   188   2012.5

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  • A novel autocrine-paracrine loop of TSLP in atopic dermatitis is modulated by p63 Reviewed

    Terufumi Kubo, Rui Ye, Shihoko Ara, Hiroshi Matsumiya, Takashi Kojima, Tomoki Kikuchi, Noriyuki Sato, Shingo Ichimiya

    JOURNAL OF IMMUNOLOGY   188   2012.5

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  • Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients Reviewed

    Hidekazu Kameshima, Tetsuhiro Tsuruma, Toshihiko Torigoe, Akari Takahashi, Yoshihiko Hirohashi, Yasuaki Tamura, Tomohide Tsukahara, Shingo Ichimiya, Takayuki Kanaseki, Yuji Iwayama, Noriyuki Sato, Koichi Hirata

    CANCER SCIENCE   102 ( 6 )   1181 - 1187   2011.6

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  • Anti-CADM-140 Antibody-positive Juvenile Dermatomyositis with Rapidly Progressive Interstitial Lung Disease and Cardiac Involvement Reviewed

    Nodoka Sakurai, Kazushige Nagai, Hiroyuki Tsutsumi, Shingo Ichimiya

    JOURNAL OF RHEUMATOLOGY   38 ( 5 )   963 - 965   2011.5

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  • Arachidonate 5-Lipoxygenase Establishes Adaptive Humoral Immunity by Controlling Primary B Cells and Their Cognate T-Cell Help Reviewed

    Tsutomu Nagashima, Shingo Ichimiya, Tomoki Kikuchi, Yoshiyuki Saito, Hiroshi Matsumiya, Shihoko Ara, Shigeru Koshiba, Jun Zhang, Chizuru Hatate, Akiko Tonooka, Terufumi Kubo, Rui Carrie Ye, Bungo Hirose, Hideaki Shirasaki, Takashi Izumi, Tsuyoshi Takami, Tetsuo Himi, Noriyuki Sato

    AMERICAN JOURNAL OF PATHOLOGY   178 ( 1 )   222 - 232   2011.1

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  • Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-alpha via distinct NF-kappa B pathways in human nasal epithelial cells Reviewed

    Tsuyoshi Ohkuni, Takashi Kojima, Noriko Ogasawara, Tomoyuki Masaki, Jun Fuchimoto, Ryuta Kamekura, Jun-ichi Koizumi, Shingo Ichimiya, Masaki Murata, Satoshi Tanaka, Tetsuo Himi, Norimasa Sawada

    TOXICOLOGY AND APPLIED PHARMACOLOGY   250 ( 1 )   29 - 38   2011.1

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    DOI： 10.1016/j.taap.2010.09.023

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  • Arachidonate 5-Lipoxygenase Establishes Adaptive Humoral Immunity by Controlling Primary B Cells and Follicular B Helper T Cells Reviewed

    Tsutomu Nagashima, Shingo Ichimiya, Shigeru Koshibal, Hiroshi Matsumiya, Shihoko Ara, Terufumi Kubo, Noriyuki Sato, Tetsuo Himi

    RECENT ADVANCES IN TONSILS AND MUCOSAL BARRIERS OF THE UPPER AIRWAYS   72   184 - 184   2011

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  • 新たな甲状腺乳頭癌特異的バイオマーカーSNX5の意義とその臨床応用

    荒 志保子, 一宮 慎吾, 菊地 智樹, 松宮 弘, 高野 善英, 外岡 暁子, 今 信一郎, 長谷川 匡, 氷見 徹夫, 佐藤 昇志

    日本病理学会会誌   99 ( 1 )   331 - 331   2010.3

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  • Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-kappa B in dendritic cells Reviewed

    Ryuta Kamekura, Takashi Kojima, Akira Takashima, Jun-ichi Koizumi, Noriko Ogasawara, Mitsuru Go, Ken-ichi Takano, Masaki Murata, Satoshi Tanaka, Shingo Ichimiya, Tetsuo Himi, Norimasa Sawada

    HISTOCHEMISTRY AND CELL BIOLOGY   133 ( 3 )   339 - 348   2010.3

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  • Induction of JAM-A during differentiation of human THP-1 dendritic cells Reviewed

    Noriko Ogasawara, Takashi Kojima, Mitsuru Go, Jun Fuchimoto, Ryuta Kamekura, Jun-ichi Koizumi, Tsuyoshi Ohkuni, Tomoyuki Masaki, Masaki Murata, Satoshi Tanaka, Shingo Ichimiya, Tetsuo Himi, Norimasa Sawada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   389 ( 3 )   543 - 549   2009.11

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  • 新たな甲状腺癌特異的バイオマーカーの生物学的意義とその臨床応用(A novel marker specific for detecting thyroid cancer: immunohistochemical analysis and biological implication)

    菊地 智樹, 一宮 慎吾, 長島 勉, 外岡 暁子, 高野 善英, 長谷川 匡, 氷見 徹夫, 佐藤 昇志

    日本癌学会総会記事   68回   355 - 355   2009.8

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  • Molecular pathological approaches to human tumor immunology Reviewed

    Noriyuki Sato, Yoshihiko Hirohashi, Tomohide Tsukahara, Tomoki Kikuchi, Hiroeki Sahara, Kenjiro Kamiguchi, Shingo Ichimiya, Yasuaki Tamura, Toshihiko Torigoe

    PATHOLOGY INTERNATIONAL   59 ( 4 )   205 - 217   2009.4

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    菊地 智樹, 一宮 慎吾, 長島 勉, 外岡 暁子, 長谷川 匡, 氷見 徹夫, 佐藤 昇志

    日本病理学会会誌   98 ( 1 )   233 - 233   2009.3

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  • Wild-type AIRE cooperates with p63 in HLA class II expression of medullary thymic stromal cells Reviewed

    Akiko Tonooka, Terufumi Kubo, Shingo Ichimiya, Yutaka Tamura, Tanja Ilmarinen, Ismo Ulmanen, Sachiko Kimura, Shigeaki Yokoyama, Yoshihide Takano, Tomoki Kikuchi, Noriyuki Sato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   379 ( 3 )   765 - 770   2009.2

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  • Scythe/BAT3 regulates apoptotic cell death induced by papillomavirus binding factor in human osteosarcoma Reviewed

    Tomohide Tsukahara, Shigeharu Kimura, Shingo Ichimiya, Toshihiko Torigoe, Satoshi Kawaguchi, Takuro Wada, Toshihiko Yamashita, Noriyuki Sato

    CANCER SCIENCE   100 ( 1 )   47 - 53   2009.1

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  • p63 Induces CD4(+) T-Cell Chemoattractant TARC/CCL17 in Human Epithelial Cells Reviewed

    Terufumi Kubo, Shingo Ichimiya, Akiko Tonooka, Tsutomu Nagashima, Tomoki Kikuchi, Noriyuki Sato

    JOURNAL OF INTERFERON AND CYTOKINE RESEARCH   28 ( 12 )   725 - 732   2008.12

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  • Prognostic impact and immunogenicity of a novel osteosarcoma antigen, papillomavirus binding factor, in patients with osteosarcoma Reviewed

    Tomohide Tsukahara, Satoshi Kawaguchi, Toshihiko Torigoe, Shigeharu Kimura, Masaki Murase, Shingo Ichimiya, Takuro Wada, Mitsunori Kaya, Satoshi Nagoya, Takeshi Ishii, Shin-ichiro Tatezaki, Toshihiko Yamashita, Noriyuki Sato

    CANCER SCIENCE   99 ( 2 )   368 - 375   2008.2

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  • The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell lymphoma (vol 7, pg 229, 2007) Reviewed

    Koh-ichi Sakata, Masanori Someya, Mutsuko Omatsu, Hiroko Asanuma, Tadashi Hasegawa, Shingo Ichimiya, Masato Hareyama, Tetsuo Himi

    BMC CANCER   8   2008.2

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  • Tonsillar crypt epithelium of palmoplantar pustulosis secretes interleukin-6 to support B-cell development via p63/p73 transcription factors Reviewed

    S. Koshiba, S. Ichimiya, T. Nagashima, A. Tonooka, T. Kubo, T. Kikuchi, T. Himi, N. Sato

    JOURNAL OF PATHOLOGY   214 ( 1 )   75 - 84   2008.1

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  • The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell lymphoma Reviewed

    Koh-ichi Sakata, Masanori Someya, Mutsuko Omatsu, Hiroko Asanuma, Tadashi Hasegawa, Masato Hareyama, Tetsuo Himi

    BMC CANCER   7   229   2007.12

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  • Induction of claudins in passaged hTERT-transfected human nasal epithelial cells with an extended life span Reviewed

    Makoto Kurose, Takashi Kojima, Jun-Ichi Koizumi, Ryuta Kamekura, Takafumi Ninomiya, Masaki Murata, Shingo Ichimiya, Makoto Osanai, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

    CELL AND TISSUE RESEARCH   330 ( 1 )   63 - 74   2007.10

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  • マントル領域B細胞におけるALOX5の役割

    齋藤 由幸, 一宮 慎吾, 小柴 茂, 外岡 暁子, 久保 輝文, 大黒 浩, 佐藤 昇志

    日本病理学会会誌   96 ( 1 )   188 - 188   2007.2

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  • Mapping of susceptibility and protective loci for acute GVHD in unrelated HLA-matched bone marrow transplantation donors and recipients using 155 microsatellite markers on chromosome 22 Reviewed

    Tomoki Kikuchi, Taeko K. Naruse, Makoto Onizuka, Suyun Li, Tetsuaki Kimura, Akira Oka, Yasuo Morishima, Jerzy K. Kulski, Shingo Ichimiya, Noriyuki Sato, Hidetoshi Inoko

    IMMUNOGENETICS   59 ( 2 )   99 - 108   2007.2

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  • Cellular networks of human thymic medullary stromas coordinated by p53-related transcription factors Reviewed

    Shingo Ichimiya, Takashi Kojima

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   54 ( 11 )   1277 - 1289   2006.11

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    DOI： 10.1369/jhc.6A7028.2006

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  • 掌蹠膿疱症における扁桃陰窩上皮の機能解析

    小柴 茂, 一宮 慎吾, 外岡 暁子, 佐藤 昇志, 氷見 徹夫

    耳鼻咽喉科免疫アレルギー   24 ( 2 )   53 - 53   2006.9

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  • 胸腺p53ファミリーによるT細胞選択とトレランス

    一宮 慎吾, 小柴 茂, 外岡 暁子, 菊地 智樹, 齋藤 由幸, 佐藤 昇志

    基盤的癌免疫研究会総会抄録   10回   75 - 75   2006.6

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  • 胸腺髄質上皮細胞におけるAIRE/p63複合体の機能的意義

    久保 輝文, 一宮 慎吾, 小柴 茂, 外岡 暁子, 小島 隆, 佐藤 昇志

    日本病理学会会誌   95 ( 1 )   391 - 391   2006.4

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  • 胸腺上皮に発現するAIRE/p63複合体による中枢性免疫寛容獲得のメカニズム

    外岡 暁子, 一宮 慎吾, 小柴 茂, 久保 輝文, 菊地 智樹, 木村 幸子, 横山 繁昭, 佐藤 昇志

    日本病理学会会誌   95 ( 1 )   199 - 199   2006.4

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  • 胸腺上皮ストローマのネットワーク形成と免疫機能調節機構

    一宮 慎吾, 外岡 暁子, 小柴 茂, 菊地 智樹, 久保 輝文, 小島 隆, 佐藤 昇志

    日本病理学会会誌   95 ( 1 )   199 - 199   2006.4

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  • 掌蹠膿疱症における扁桃陰窩上皮の機能解析

    小柴 茂, 一宮 慎吾, 外岡 暁子, 氷見 徹夫, 佐藤 昇志

    日本病理学会会誌   95 ( 1 )   290 - 290   2006.4

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  • Current progress and perspectives for human tumor immunotherapy

    Sato Noriyuki, Hirohashi Yoshihiko, Kamiguchi Kenjiro, Ichimiya Shingo, Sahara Hiroeki, Hirata Koichi, Tsukamoto Taiji, Yamashita Toshihiko, Torigoe Toshihiko

    Tumor Research   41   1 - 13   2006

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  • p53関連分子による胸腺ストローマの細胞間結合制御

    小柴 茂, 一宮 慎吾, 小島 隆, 外岡 暁子, 村田 雅樹, 木村 幸子, 横山 繁昭, 氷見 徹夫, 佐藤 昇志

    日本免疫学会総会・学術集会記録   35   65 - 65   2005.11

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  • AIRE-1およびp53ファミリーによるMHCクラスII分子発現調節機構

    外岡 暁子, 一宮 慎吾, 小柴 茂, 木村 幸子, 横山 繁昭, 佐藤 昇志

    日本免疫学会総会・学術集会記録   35   65 - 65   2005.11

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  • p63,p73転写因子による胸腺上皮細胞の機能調節機構

    外岡 暁子, 一宮 慎吾, 小柴 茂, 木村 幸子, 横山 繁昭, 佐藤 昌明, 佐藤 昇志

    日本病理学会会誌   94 ( 1 )   219 - 219   2005.3

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  • 胸腺ストローマの細胞間結合とその制御

    小柴 茂, 一宮 慎吾, 小島 隆, 村田 雅樹, 外岡 暁子, 木村 幸子, 横山 繁昭, 氷見 徹夫, 佐藤 昇志

    日本病理学会会誌   94 ( 1 )   367 - 367   2005.3

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  • Napsin A is useful to distinguish primary lung adenocarcinoma from adenocarcinomas of other organs Reviewed

    A Suzuki, N Shijubo, G Yamada, S Ichimiya, M Satoh, S Abe, N Sato

    PATHOLOGY RESEARCH AND PRACTICE   201 ( 8-9 )   579 - 586   2005

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    DOI： 10.1016/j.prp.2005.05.010

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  • 胸腺スカフォールドの組織構築とその制御

    小柴 茂, 一宮 慎吾, 小島 隆, 近藤 伸彦, 外岡 暁子, 村田 雅樹, 高桑 麗子, 横山 繁昭, 氷見 徹夫, 佐藤 昇志

    日本免疫学会総会・学術集会記録   34   72 - 72   2004.11

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  • 胸腺上皮細胞におけるHLA分子の発現制御機構

    外岡 暁子, 一宮 慎吾, 小柴 茂, 近藤 伸彦, 上口 権二郎, 田村 保明, 鳥越 俊彦, 池田 英之, 高桑 麗子, 横山 繁昭, 佐藤 昌明, 佐藤 昇志

    日本免疫学会総会・学術集会記録   34   72 - 72   2004.11

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  • サルコイドーシス(サ症)のTh1反応におけるオステオポンチンの意義の検討

    四十坊 典晴, 市村 志保, 重原 克則, 猪股 慎一郎, 山田 玄, 一宮 慎吾, 阿部 庄作, 佐藤 昇志, 平賀 洋明

    サルコイドーシス/肉芽腫性疾患   24 ( Suppl. )   48 - 48   2004.10

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  • Role of the p38 MAP-kinase signaling pathway for Cx32 and claudin-1 in the rat liver Reviewed

    Takashi Kojima, Toshinobu Yamamoto, Masaki Murata, Mengdong Lan, Ken-Ichi Takano, Mitsuru Go, Shingo Ichimiya, Hideki Chiba, Norimasa Sawada

    Cell Communication and Adhesion   10 ( 4-6 )   437 - 443   2003.7

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  • 頭蓋咽頭腫におけるp53ファミリーの発現とその意義

    百田 洋之, 一宮 慎吾, 池田 健, 八巻 稔明, 宝金 清博, 佐藤 昇志

    Brain Tumor Pathology   20 ( Suppl. )   59 - 59   2003.5

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  • Improved generation of HLA class I/peptide tetramers Reviewed

    Y Sato, H Sahara, T Tsukahara, M Kondo, Y Hirohashi, Y Nabeta, S Kawaguchi, H Ikeda, T Torigoe, S Ichimiya, Y Tamura, T Wada, T Yamashita, M Goto, H Takasu, N Sato

    JOURNAL OF IMMUNOLOGICAL METHODS   271 ( 1-2 )   177 - 184   2002.12

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    DOI： 10.1016/s0022-1759(02)00329-0

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  • 原発性肺癌患者におけるClara cell 10kilodalton protein(CC10)遺伝子多型についての検討

    大地 貴, 四十坊 典晴, 山田 玄, 阿部 庄作, 山口 昭弘, 一宮 慎吾, 佐藤 昇志, 河端 薫雄, 伊藤 喜久

    肺癌   42 ( 5 )   412 - 412   2002.10

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  • Comparative analysis of the structure and chromosomal assignment of CD1: an evidence for different evolutionary histories between classic CD1 and CD1D class genes Reviewed

    A Matsuura, M Kinebuchi, S Katabami, HZ Chen, K Kasai, S Ichimiya, K Yamada, MC Yoshida, M Horie, N Sato

    JOURNAL OF EXPERIMENTAL ANIMAL SCIENCE   41 ( 1-2 )   87 - 90   2000.3

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  • The role of non-classical MHC class I molecules Invited

    Matsuura A, Kinebuchi M, Chen HZ, Ichimiya S, Kasai K

    Rinsho-Menneki (Clinical Immunology: Japan)   30   1376 - 1384   1998

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  • Interaction of DA41, a DAN-binding protein, with the epidermal growth factor-like protein, S(1-5) Reviewed

    T Ozaki, K Kondo, Y Nakamura, S Ichimiya, A Nakagawara, S Sakiyama

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   237 ( 2 )   245 - 250   1997.8

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  • Expression of CD1 molecules but not authentic TL antigens by rat thymus: Possible functional substitution between class Ib molecules in the thymu Reviewed

    Matsuura A, Takayama S, Kinebuchi M, Hashimoto Y, Kasai K, Kozutsumi D, Ichimiya S, Honda R, Natori T, Kikuchi K

    Proceedings of International Symposium on Evolution of Network and Molecular Information   1996

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  • A new mAb 3B6 distingnishes a novel subpopulation from adult rat bone marrow cells. Reviewed

    Matsuura A, Kinebuchi M, Ichimiya S, Hashimoto Y, Shen M, Katabami S, Kikuchi K

    Proceedings of Xth International Workshop on alloantigenic systems in the Rat   10   1994

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  • MOLECULAR-CLONING OF A CDNA-ENCODING THE RAT HOMOLOG OF CD1 Reviewed

    S ICHIMIYA, A MATSUURA, S TAKAYAMA, K KIKUCHI

    TRANSPLANTATION PROCEEDINGS   25 ( 5 )   2773 - 2774   1993.10

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  • Improvement of expression cloning method using Cell sorter - Cloning of rat CD8 α chain cDNA Reviewed

    Onodera K, Matsuura A, Kon S, Murakami T, Takayama S, Ichimiya S, Kikuchi K

    Proceedings of the Japanese Society for Immunology   21   285   1991

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  • Tla gene and its expression in rat Reviewed

    Takayama S, Ichimiya S, Matsuura A, Kikuchi K

    Proceedings of the Japanese Society for Immunology   21   465   1991

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MISC

  • IgG4 関連疾患の免疫病態と治療への展望.

    亀倉 隆太, 一宮 慎吾

    リウマチ科   64   559 - 566   2020

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  • T細胞サブセットの病理学

    一宮 慎吾

    日本病理学会会誌   107 ( 1 )   279 - 279   2018.4

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  • 免疫学の進歩と神経免疫学への応用 濾胞ヘルパーT細胞の機能異常と免疫関連疾患

    一宮 慎吾, 亀倉 隆太

    神経免疫学   22 ( 1 )   66 - 66   2017.10

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  • 血管炎・その他の免疫疾患 IgG4関連涙腺唾液腺炎の病変部位とリンパ組織に存在する濾胞ヘルパーT細胞の機能的差異

    亀倉 隆太, 高野 賢一, 山本 元久, 伊藤 史恵, 川田 耕司, 重原 克則, 高橋 裕樹, 氷見 徹夫, 一宮 慎吾

    アレルギー   66 ( 4-5 )   622 - 622   2017.5

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  • アトピー性皮膚炎表皮におけるNF-κBを介したΔNp73によるTSLPの産生制御

    熊谷 綾子, 川田 耕司, 亀倉 隆太, 澄川 靖之, 一宮 慎吾, 山下 利春

    日本皮膚科学会雑誌   127 ( 5 )   1175 - 1175   2017.5

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  • 成人喘息 病態 アトピー型喘息における末梢血濾胞ヘルパーT細胞の活性化と治療における変化の検討

    重原 克則, 宮島 さつき, 亀倉 隆太, 川田 耕司, 高橋 弘毅, 一宮 慎吾

    アレルギー   66 ( 4-5 )   574 - 574   2017.5

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  • 好酸球、T細胞、抗原提示細胞 間質性肺炎患者における濾胞性ヘルパーT細胞サブセットについての前向き観察研究

    浅井 悠一郎, 近藤 瞬, 角 俊行, 田中 悠祐, 錦織 博貴, 宮島 さつき, 千葉 弘文, 高橋 弘彦, 亀倉 隆太, 川田 耕司, 一宮 慎吾, 重原 克則

    アレルギー   66 ( 4-5 )   595 - 595   2017.5

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  • IgG4関連涙腺・唾液腺の病変部位におけるIgG4産生機構の解明

    伊藤 史恵, 亀倉 隆太, 川田 耕司, 高野 賢一, 氷見 徹夫, 一宮 慎吾

    日本病理学会会誌   106 ( 1 )   324 - 324   2017.3

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  • シラカバ花粉症の病態形成における血液濾胞ヘルパーT細胞の役割

    亀倉 隆太, 實川 純人, 長屋 朋典, 川田 耕司, 重原 克則, 一宮 慎吾, 氷見 徹夫

    耳鼻咽喉科免疫アレルギー   34 ( 2 )   48 - 49   2016.6

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  • アトピー性皮膚炎表皮におけるTSLPの発現はΔNp73に依存する

    熊谷 綾子, 山下 利春, 川田 耕司, 亀倉 隆太, 一宮 慎吾

    日本皮膚科学会雑誌   126 ( 7 )   1325 - 1325   2016.6

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  • 咳喘息患者における末梢血濾胞ヘルパーT細胞と制御性B細胞の検討

    重原 克則, 亀倉 隆太, 川田 耕司, 一宮 慎吾

    アレルギー   65 ( 4-5 )   629 - 629   2016.5

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  • 濾胞ヘルパーT細胞の分化と機能における脂質メディエーターの役割

    長屋 朋典, 亀倉 隆太, 山下 恵司, 實川 純人, 川田 耕司, 一宮 慎吾, 氷見 徹夫

    日本耳鼻咽喉科学会会報   119 ( 4 )   639 - 639   2016.4

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  • 咳喘息患者における末梢血濾胞ヘルパーT細胞と抑制性B細胞の検討

    重原 克則, 亀倉 隆太, 宮島 さつき, 川田 耕司, 高橋 弘毅, 一宮 慎吾

    日本呼吸器学会誌   5 ( 増刊 )   291 - 291   2016.3

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  • ヒト口蓋扁桃に存在する濾胞ヘルパーT細胞の機能制御機構の解明

    山下 恵司, 川田 耕司, 實川 純人, 長屋 朋典, 松宮 弘, 亀倉 隆太, 一宮 慎吾, 氷見 徹夫

    日本耳鼻咽喉科学会会報   118 ( 4 )   508 - 508   2015.4

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    DOI： 10.3950/jibiinkoka.118.508

    Ichushi

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  • Role of follicular helper T cell subsets in development of human diseases

    63 ( 3 )   214 - 217   2015.3

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    CiNii Research

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  • 2型濾胞ヘルパーT細胞と制御性B細胞はアレルギー性鼻炎から気管支喘息への移行に関与している

    亀倉 隆太, 重原 克則, 實川 純人, 川田 耕司, 氷見 徹夫, 一宮 慎吾

    日本病理学会会誌   104 ( 1 )   452 - 452   2015.3

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  • 甲状腺癌発生におけるソーティングネキシン5の機能的意義

    實川 純人, 亀倉 隆太, 川田 耕司, 熊谷 綾子, 佐藤 明紀, 長屋 朋典, 山下 恵司, 氷見 徹夫, 一宮 慎吾

    日本病理学会会誌   104 ( 1 )   391 - 391   2015.3

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  • リンパ管内皮細胞のリンパ管管腔形成におけるレプチンの役割

    佐藤 明紀, 亀倉 隆太, 川田 耕司, 川田 将也, 山下 恵司, 實川 純人, 熊谷 綾子, 佐藤 昇志, 一宮 慎吾

    日本病理学会会誌   104 ( 1 )   381 - 381   2015.3

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  • アレルギー性鼻炎の病態形成におけるエピイムノームの役割. 特集 アレルギー疾患ガイドラインダイジェストに寄せる

    亀倉 隆太, 氷見 徹夫, 一宮 慎吾

    アレルギーの臨床   35   57 - 63   2015

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    長屋朋典, 亀倉隆太, 山下恵司, 實川純人, 関伸彦, 川田耕司, 一宮慎吾, 氷見徹夫

    口腔・咽頭科   27 ( 3 )   344   2014.8

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  • 濾胞ヘルパーT細胞(Tfh細胞)の分化機構と免疫病態との関連

    長屋朋典, 亀倉隆太, 山下恵司, 三橋由佳梨, 實川純人, 長島勉, 熊谷綾子, 関伸彦, 氷見徹夫, 一宮慎吾

    日本病理学会会誌   103 ( 1 )   246   2014.3

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  • アトピー性皮膚炎の表皮におけるp53ファミリー分子の機能的意義

    熊谷綾子, 山下恵司, 長屋朋典, 山下利春, 一宮慎吾

    日本病理学会会誌   103 ( 1 )   267   2014.3

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  • リンパ管内皮細胞の形成におけるレプチンの役割

    佐藤明紀, 山下恵司, 三橋由佳梨, 長屋朋典, 熊谷綾子, 佐藤昇志, 一宮慎吾

    日本病理学会会誌   103 ( 1 )   256   2014.3

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  • 濾胞ヘルパーT細胞による抗体産生プログラムの制御機構

    山下恵司, 長屋朋典, 三橋由佳梨, 實川純人, 亀倉隆太, 熊谷綾子, 関伸彦, 氷見徹夫, 一宮慎吾

    日本病理学会会誌   103 ( 1 )   247   2014.3

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  • 濾胞ヘルパーT細胞の分化機構と免疫病態との関連

    長屋朋典, 亀倉隆太, 山下恵司, 三橋由佳梨, 長島勉, 松宮弘, 一宮慎吾, 氷見徹夫

    日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集   32nd   121   2014

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  • POU2AF1による扁桃濾胞ヘルパーT細胞の機能調節機構

    山下恵司, 松宮弘, 三橋由佳梨, 長屋朋典, 亀倉隆太, 関伸彦, 一宮慎吾, 氷見徹夫

    日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集   32nd   102   2014

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  • 扁桃・アデノイドはなぜあるのか?鼻はなにをしているのか?―小児の粘膜免疫・粘膜防御最前線―

    氷見徹夫, 高野賢一, 山下恵司, 小笠原徳子, 正木智之, 小幡和史, 堤裕幸, 小島隆, 一宮慎吾, 澤田典均, 横田伸一

    小児耳鼻咽喉科   34 ( 3 )   239 - 244   2013.12

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  • T<sub>FH</sub>細胞とメモリーB細胞

    一宮慎吾, 山下恵司, 長屋朋典, 三橋由佳梨, 松宮弘, 長島勉, 関伸彦, 氷見徹夫

    月刊臨床免疫・アレルギー科   60 ( 5 )   576 - 580   2013.11

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  • 濾胞ヘルパーT細胞を調節するPOU2AF1の機能的意義

    山下恵司, 松宮弘, 三橋由佳梨, 関伸彦, 佐藤昇志, 氷見徹夫, 一宮慎吾

    日本病理学会会誌   102 ( 1 )   331   2013.4

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  • 進行性筋萎縮症(PMA)の1剖検例における異常TDP‐43

    山内理香, 山本大輔, 岩原直敏, 津田玲子, 松村晃寛, 鈴木秀一郎, 津田笑子, 保月隆良, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 杉本幸太郎, 一宮慎吾, 長谷川匡

    臨床神経学   52 ( 3 )   199   2012.3

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  • O58-3 アトピー型気管支喘息患者における血清IL-9の検討(サイトカイン・ケモカイン1,口演,第62回日本アレルギー学会秋季学術大会)

    重原 克則, 伊藤 進, 井上 祐二, 一宮 慎吾

    アレルギー   61 ( 9-10 )   1541   2012

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    Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

    DOI： 10.15036/arerugi.61.1541_1

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  • P2-072  アトピー性皮膚炎の表皮におけるp63依存性TSLP-TSLP受容体経路

    久保 輝文, 叶 汭, 三橋 由佳梨, 山下 恵司, 佐藤 明紀, 小島 隆, 佐藤 昇志, 一宮 慎吾

    日本臨床免疫学会会誌   35 ( 4 )   362b - 362b   2012

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    アトピー性皮膚炎は本邦の小児の約1割が罹患し，罹患者の生活の質を著しく低下させる．さらにアトピー性皮膚炎自体が気管支喘息やアレルギー性結膜炎など種々の慢性アレルギー疾患の根底にある可能性が分子免疫学的にも支持されつつあり，その病態の機序の解明が急がれている．   近年，アトピー性皮膚炎の患部のケラチノサイトがthymic stromal lymphopoietin（TSLP）を高産生することが明らかとなった．TSLPはTSLP受容体（TSLPR）を発現する樹状細胞を介してTh0細胞をTh2細胞へと分化させることで，アトピー・アレルギー疾患の病態形成に中心的役割を果たすと考えられている．   我々は今回，表皮ケラチノサイトにおけるTSLPRの発現を明らかとした．また，表皮ケラチノサイト初代培養細胞および表皮モデルHaCaT細胞を用いた検討において，TSLPRの発現は表皮幹細胞因子p63を介した自然免疫経路によって制御されていた．興味深いことに表皮に対するTSLP刺激は更なるTSLP産生を惹起し，その他の炎症性サイトカインの発現も促進していた．これらの結果からTSLPはオートクラインあるいはパラクラインによってケラチノサイト自身にも作用するループを形成し，アトピー性皮膚炎患部表皮の炎症環境の形成，維持に関与していると考えられる．

    DOI： 10.2177/jsci.35.362b

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  • 症例解説-リンパ節 マントル細胞リンパ腫の病理組織診断

    一宮 慎吾

    病理と臨床 27   1094 - 1095   2009

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  • JNK特異的阻害剤による免疫抑制の可能性とその機序

    宮島 正博, 森川 雅之, 田畑 哲寿, 一宮 慎吾, 佐藤 昇志, 安倍 十三夫

    日本外科学会雑誌   107 ( 2 )   709 - 709   2006.3

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  • Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma

    H Kojima, N Shijubo, G Yamada, S Ichimiya, S Abe, M Satoh, N Sato

    CANCER   104 ( 8 )   1668 - 1677   2005.10

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  • 重症筋無力症の胸腺におけるCHRNA9遺伝子の発現(縦隔腫瘍 (3), 第22回日本呼吸器外科学会総会)

    小柳 哲也, 渡辺 敦, 馬渡 徹, 安倍 十三夫, 一宮 慎吾

    日本呼吸器外科学会雑誌   19 ( 3 )   374 - 374   2005.5

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    Language：Japanese   Publisher：特定非営利活動法人日本呼吸器外科学会  

    DOI： 10.2995/jacsurg.19.374_4

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  • Effects of inhaled FK 506 on the suppression of acute rejection after lung transplantation: Use of a rat orthotopic lung transplantation model

    A Ingu, K Komatsu, S Ichimiya, N Sato, Y Hirayama, M Morikawa, T Abe

    JOURNAL OF HEART AND LUNG TRANSPLANTATION   24 ( 5 )   538 - 543   2005.5

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  • HLA-DR- and CD11c-positive dendritic cells penetrate beyond well-developed epithelial tight junctions in human nasal mucosa of allergic rhinitis

    K Takano, T Kojima, M Go, M Murata, S Ichimiya, T Himi, N Sawada

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   53 ( 5 )   611 - 619   2005.5

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  • A calcium binding protein, S100A4, mediates T cell dependent cytotoxicity as a transformation-associated antigen

    N Kondo, S Ichimiya, Y Tamura, A Tonooka, S Koshiba, T Torigoe, K Kamiguchi, K Takenaga, N Sato

    MICROBIOLOGY AND IMMUNOLOGY   49 ( 1 )   49 - 56   2005

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  • Expression and function of tight junctions in the crypt epithelium of human palatine tonsils

    M Go, T Kojima, K Takano, M Murata, S Ichimiya, H Tsubota, T Himi, N Sawada

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   52 ( 12 )   1627 - 1638   2004.12

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  • Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute

    K Ida, S Kawaguchi, Y Sato, T Tsukahara, Y Nabeta, H Sahara, H Ikeda, T Torigoe, S Ichimiya, K Kamiguchi, T Wada, S Nagoya, H Hiraga, A Kawai, T Ishii, N Araki, A Myoui, S Matsumoto, T Ozaki, H Yoshikawa, T Yamashita, N Sato

    JOURNAL OF IMMUNOLOGY   173 ( 2 )   1436 - 1443   2004.7

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  • Expression profiles and functional implications of p53-like transcription factors in thymic epithelial cell subtypes

    T Kikuchi, S Ichimiya, T Kojima, L Crisa, S Koshiba, A Tonooka, N Kondo, PT van der Saag, S Yokoyama, N Sato

    INTERNATIONAL IMMUNOLOGY   16 ( 6 )   831 - 841   2004.6

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  • Tumor-derived heat shock protein 70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity

    G Ueda, Y Tamura, Hirai, I, K Kamiguchi, S Ichimiya, T Torigoe, H Hiratsuka, H Sunakawa, N Sato

    CANCER SCIENCE   95 ( 3 )   248 - 253   2004.3

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  • Polymorphism of Clara cell 10-kD protein gene of sarcoidosis

    T Ohchi, N Shijubo, Kawabata, I, S Ichimiya, S Inomata, A Yamaguchi, Y Umemori, Y Itoh, S Abe, Y Hiraga, N Sato

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   169 ( 2 )   180 - 186   2004.1

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  • Inhibition of MAP kinase activity moderates changes in expression and function of Cx32 but not claudin-1 during DNA synthesis in primary cultures of rat hepatocytes

    Takashi Kojima, Toshinobu Yamamoto, Mengdong Lan, Masaki Murata, Ken-Ichi Takano, Mitsuru Go, Shingo Ichimiya, Hideki Chiba, Norimasa Sawada

    Medical Electron Microscopy   37 ( 2 )   101 - 113   2004

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    Language：English   Publisher：Springer Japan  

    DOI： 10.1007/s00795-003-0239-7

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  • 胸腺上皮細胞機能を制御する分子群

    臨床免疫   2004

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  • Molecules regulating the function of thymic epithelial cells

    Clinical Immunology   2004

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  • Chymase-positive mast cells in small sized adenocarcinoma of the lung

    M Nagata, N Shijubo, AF Walls, S Ichimiya, S Abe, N Sato

    VIRCHOWS ARCHIV   443 ( 4 )   565 - 573   2003.10

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  • Histone H2AX sensitizes glioma cells to genotoxic stimuli by recruiting DNA double-strand break repair proteins

    H Momota, S Ichimiya, N Kondo, T Kikuchi, T Torigoe, T Yamaki, K Houkin, N Sato

    INTERNATIONAL JOURNAL OF ONCOLOGY   23 ( 2 )   311 - 315   2003.8

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  • Role of the p38 MAP-kinase signaling pathway for Cx32 and claudin-1 in the rat liver

    T Kojima, T Yamamoto, M Murata, M Lan, KI Takano, M Go, S Ichimiya, H Chiba, N Sawada

    CELL COMMUNICATION AND ADHESION   10 ( 4-6 )   437 - 443   2003.7

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  • Frequent beta-catenin alteration in gallbladder carcinomas

    Y Kimura, T Furuhata, M Mukaiya, C Kihara, M Kawakami, K Okita, Y Yanai, H Zenbutsu, M Satoh, S Ichimiya, K Hirata

    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH   22 ( 2 )   321 - 328   2003.6

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  • Rapidly growing early gastric cancer with microsatellite instability

    K Yamashita, N Kato, H Takahashi, H Shimizu, H Suzuki, S Motoya, Y Arimura, T Endo, H Ura, S Ichimiya, K Imai

    JOURNAL OF GASTROENTEROLOGY   38 ( 2 )   170 - 174   2003.2

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  • Immunohistochemical analysis of the p53 family members in human craniopharyngiomas

    Hiroyuki Momota, Shingo Ichimiya, Tatsuru Ikeda, Toshiaki Yamaki, Tomoki Kikuchi, Kiyohiro Houkin, Noriyuki Sato

    Brain Tumor Pathology   20 ( 2 )   73 - 77   2003

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  • T-cell receptor variable gamma chain gene expression in the interaction between rat gamma delta-type T cells and heat-shock protein 70-like molecule

    T Ichinohe, S Ichimiya, A Kishi, Y Tamura, N Kondo, G Ueda, T Torigoe, A Yamaguchi, H Hiratsuka, Hirai, I, G Kohama, N Sato

    MICROBIOLOGY AND IMMUNOLOGY   47 ( 5 )   351 - 357   2003

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  • Improved generation of HLA class I/peptide tetramers

    Y Sato, H Sahara, T Tsukahara, M Kondo, Y Hirohashi, Y Nabeta, S Kawaguchi, H Ikeda, T Torigoe, S Ichimiya, Y Tamura, T Wada, T Yamashita, M Goto, H Takasu, N Sato

    JOURNAL OF IMMUNOLOGICAL METHODS   271 ( 1-2 )   177 - 184   2002.12

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  • Detection and induction of CTLs specific for SYT-SSX-derived peptides in HLA-A24(+) patients with synovial sarcoma

    Y Sato, Y Nabeta, T Tsukahara, Y Hirohashi, R Syunsui, A Maeda, H Sahara, H Ikeda, T Torigoe, S Ichimiya, T Wada, T Yamashita, H Hiraga, A Kawai, T Ishii, N Araki, A Myoui, S Matsumoto, T Umeda, S Ishii, S Kawaguchi, N Sato

    JOURNAL OF IMMUNOLOGY   169 ( 3 )   1611 - 1618   2002.8

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  • A gene encoding human gastric signet ring cell carcinoma antigen recognized by HLA-A31-restricted cytotoxic T lymphocytes

    H Sahara, Y Nabeta, T Torigoe, Y Hirohashi, S Ichimiya, Y Wada, N Takahashi, K Jimbow, T Yajima, N Watanabe, K Kikuchi, N Sato

    JOURNAL OF IMMUNOTHERAPY   25 ( 3 )   235 - 242   2002.5

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  • p73 is expressed in human thymic epithelial cells

    S Ichimiya, T Kojima, H Momota, N Kondo, T Ozaki, A Nakagawara, ML Toribio, M Imamura, N Sato

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   50 ( 4 )   455 - 462   2002.4

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  • レーザーマイクロダイセクションを利用した免疫組織の新しい解析法

    一宮慎吾

    Annual Review 免疫2002   2002

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  • Reguratory mechanism of thymic epithelial cell function by p53 related transcription factors

    Annual Review 2003   2002

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  • Improved fixation methods for frozen section diagnosis

    Rinshokensa   2002

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  • [Genetic analysis of microdissected human tissues]

    ICHIMIYA Shingo, SATO Noriyuki

    Hokkaido Igaku Zasshi   77 ( 2 )   139 - 41   2002

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  • p53関連遺伝子による胸腺上皮細胞の機能調節

    Annual Review免疫2003   2002

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  • Examination of the Fixation Applicable to Frozen Section

    46 ( 1 )   77 - 81   2002

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  • Medicine in Postgenome Era. 1.Genetic analysis of microdissected human tissues

    Ichimiya Shingo, Satou Noriyuki

    The Hokkaido journal of medical science   77 ( 2 )   139 - 41   2002

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  • The cell surface-expressed HSC70-like molecule preferentially reacts with the rat T-cell receptor V delta 6 family

    A Kishi, T Ichinohe, Hirai, I, K Kamiguchi, Y Tamura, M Kinebuchi, T Torigoe, S Ichimiya, N Kondo, K Ishitani, T Yoshikawa, M Kondo, A Matsuura, N Sato

    IMMUNOGENETICS   53 ( 5 )   401 - 409   2001.7

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  • A case of inflammatory fibrosarcoma of the retroperitoneum

    Atsumori Ueno, Itaru Ozeki, Shigeru Sasaki, Sumio Yamaguchi, Norikazu Iwata, Hiroyuki Kaneto, Fumio Itoh, Takao Endo, Shingo Ichimiya, Masaaki Satoh, Noriyuki Otsuka, Michio Shimizu, Michiaki Matsushita, Satoru Todo, Kohzoh Imai

    Japanese Journal of Gastroenterology   98 ( 4 )   436 - 441   2001.4

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    Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

    DOI： 10.11405/nisshoshi1964.98.436

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  • Downregulation of hASH1 is associated with the retinoic acid-induced differentiation of human neuroblastoma cell lines

    S Ichimiya, Y Nimura, N Seki, T Ozaki, T Nagase, A Nakagawara

    MEDICAL AND PEDIATRIC ONCOLOGY   36 ( 1 )   132 - 134   2001.1

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  • Genetic analysis of p73 localized at chromosome 1p36.3 in primary neuroblastomas

    S Ichimiya, Y Nimura, H Kageyama, N Takada, M Sunahara, T Shishikura, Y Nakamura, S Sakiyama, N Seki, M Ohira, Y Kaneko, F McKeon, D Caput, A Nakagawara

    MEDICAL AND PEDIATRIC ONCOLOGY   36 ( 1 )   42 - 44   2001.1

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  • H2遺伝子複合体、H2ハプロタイプ、Ia、抗Ia抗体、I-A亜領域、I-E亜領域、I-J亜領域

    免疫学辞典第2版   2001

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  • H2 gene complex

    Dictionary for Immunology, second edition   2001

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  • Aberrant Wnt-wingless signaling in gallbladder carcinomas

    KIMURA Yasutoshi, FURUHATA Tomohisa, MUKAIYA Mitsuhiro, YANAI Yoshiyuki, KAWAKAMI Masayo, SATOH Masaaki, ICHIMIYA Shingo, HIRAMA Toshinori, HIRATA Koichi

    Tando   14 ( 4 )   339 - 346   2000.10

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    Language：Japanese   Publisher：Japan Biliary Association  

    To investigate the contribution of β-catenin to the development of gallbladder carcinoma, we searched for genetic alterations of the β-cetenin gene, ctnnb-1. Mutational analysis of exon 3 in ctnnb-1, which encodes the serine/threonine residues for GSK-3β phosphorylation sites was performed for 5 gallbladder cancers with pancreaticobiliary malunion, PMB and 8 noncancerous tissues with PBM. PCR-SSCP analysis showed super-shifted bands in the electrophoretic display, but no mutation was detected through nucleotide sequencing analysis near potential GSK-3βphosphorylation sites. We also performed immunohistochemical analysis of β-catenin protein in all cases, and confirmed accumulation in both the nucleus and cytoplasm in three of 5 cancer tissues, while neighboring noncancerous tissue and the biliary tissue with PBM alone displayed membrane staining. Our results indicated that abnormal Wnt-wingless signaling, resulting in β-catenin accumulations, might be involved in the malignant transformation rather than the development of gallbladder carcinomas.

    DOI： 10.11210/tando1987.14.4_339

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  • 178 乳腺小葉癌の穿刺吸引細胞診像の検討

    太田 由紀子, 東 恭悟, 浅沼 広子, 佐々木 雅博, 岸 誼博, 木村 幸子, 一宮 慎吾, 池田 健, 佐藤 昌明, 成松 英明

    日本臨床細胞学会雑誌   39 ( 2 )   445 - 445   2000.9

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  • 275 Salivary duct carcinomaの3例

    東 恭悟, 浅沼 広子, 太田 由紀子, 佐々木 雅博, 近藤 啓, 遠藤 明美, 木村 幸子, 一宮 慎吾, 池田 健, 佐藤 昌明

    日本臨床細胞学会雑誌   39 ( 2 )   494 - 494   2000.9

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  • 肝原発カルチノイド腫ようの1剖検例

    小関至, 佐々木茂, 安井寛, 岩田徳和, 三原真美, 金戸宏行, 一宮慎吾, 佐藤昌明, 今井浩三

    日本消化器病学会雑誌   97   A676   2000.9

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  • p73: Structure and function

    S Ichimiya, A Nakagawara, Y Sakuma, S Kimura, T Ikeda, M Satoh, N Takahashi, N Sato, M Mori

    PATHOLOGY INTERNATIONAL   50 ( 8 )   589 - 593   2000.8

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    DOI： 10.1046/j.1440-1827.2000.01090.x

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  • NFBD1/KIAA0170 is a novel nuclear transcriptional transactivator with BRCT domain

    T Ozaki, T Nagase, S Ichimiya, N Seki, M Ohiri, N Nomura, N Takada, S Sakiyama, BL Weber, A Nakagawara

    DNA AND CELL BIOLOGY   19 ( 8 )   475 - 485   2000.8

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  • A Case of Bizarre parosteal Osteochondromatous Proliferation of the Femur

    KAWAGUCHI S

    74 ( 6 )   S1123   2000.6

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  • Identification of the full-length KIAA0591 gene encoding a novel kinesin-related protein which is mapped to the neuroblastoma suppressor gene locus at 1p36.2

    M Nagai, S Ichimiya, T Ozaki, N Seki, M Mihara, S Furuta, M Ohira, N Tomioka, N Nomura, S Sakiyama, S Kubo, K Takakura, T Hori, A Nakagawara

    INTERNATIONAL JOURNAL OF ONCOLOGY   16 ( 5 )   907 - 916   2000.5

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  • 肺癌における,p53関連遺伝子p73の変異および欠失の解析,ならびにその臨床的意義について

    山本直敬, 飯島崇利, 砂原正男, 一宮慎吾, 影山肇, 木村秀樹, 中川原章

    日本癌学会総会記事   58th   528   1999.8

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  • A case of solitary fibrous tumor of the orbit

    53 ( 6 )   1381 - 1384   1999.6

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  • Mutational analysis of the p73 gene in human breast cancers

    T Shishikura, S Ichimiya, T Ozaki, Y Nimura, H Kageyama, Y Nakamura, S Sakiyama, M Miyauchi, N Yamamoto, M Suzuki, N Nakajima, A Nakagawara

    INTERNATIONAL JOURNAL OF CANCER   84 ( 3 )   321 - 325   1999.6

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  • Identification of a transactivation activity in the COOH-terminal region of p73 which is impaired in the naturally occurring mutants found in human neuroblastomas

    N Takada, T Ozaki, S Ichimiya, S Todo, A Nakagawara

    CANCER RESEARCH   59 ( 12 )   2810 - 2814   1999.6

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  • Multiple Orbital Neurofibromas Not Associated with von Recklinghausen's Disease

    NAKAMURA Yasushi, OHTSUKA Kenji, HASHIMOTO Masato, ICHIMIYA Singo, SATOH Masaaki

    16 ( 2 )   283 - 285   1999.2

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  • P-804 肺癌における、p53関連遺伝子p73の変異および欠失と、その臨床的意義

    山本 直敬, 飯島 崇利, 一宮 慎吾, 影山 肇, 木村 秀樹, 中川原 章

    日本外科学会雑誌   100 ( 0 )   512 - 512   1999.2

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  • O-334 p53 co-activator, p33^<ING1>の神経芽腫発生における役割 : 発現および変異とp53, mdm2との関連について

    高橋 將人, 一宮 慎吾, 藤堂 省

    日本外科学会雑誌   100 ( 0 )   191 - 191   1999.2

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  • Absence of mutation of the p73 gene localized at chromosome 1p36.3 in hepatocellular carcinoma

    M Mihara, Y Nimura, S Ichimiya, S Sakiyama, S Kajikawa, W Adachi, J Amano, A Nakagawara

    BRITISH JOURNAL OF CANCER   79 ( 1 )   164 - 167   1999.1

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  • p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent

    S Ichimiya, Y Nimura, H Kageyama, N Takada, M Sunahara, T Shishikura, Y Nakamura, S Sakiyama, N Seki, M Ohira, Y Kaneko, F McKeon, D Caput, A Nakagawara

    ONCOGENE   18 ( 4 )   1061 - 1066   1999.1

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  • p73, a gene related to p53, is not mutated in esophageal carcinomas

    Y Nimura, M Mihara, S Ichimiya, S Sakiyama, N Seki, M Ohira, N Nomura, M Fujimori, W Adachi, J Amano, M He, YM Ping, A Nakagawara

    INTERNATIONAL JOURNAL OF CANCER   78 ( 4 )   437 - 440   1998.11

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  • Mutational analysis of the p73 gene localized at chromosome 1p36.3 in colorectal carcinomas

    M Sunahara, S Ichimiya, Y Nimura, N Takada, S Sakiyama, Y Sato, S Todo, W Adachi, J Amano, A Nakagawara

    INTERNATIONAL JOURNAL OF ONCOLOGY   13 ( 2 )   319 - 323   1998.8

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  • Mutation Analysis of p73 Gene in Bone & Soft Tissue Tumor

    HANAOKA E

    72 ( 6 )   S1022   1998.6

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  • Glial cell line-derived neurotrophic factor neurturin-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret, GFR alpha-1, and GFR alpha-2

    T Hishiki, Y Nimura, E Isogai, K Kondo, S Ichimiya, Y Nakamura, T Ozaki, S Sakiyama, M Hirose, N Seki, H Takahashi, N Ohnuma, M Tanabe, A Nakagawara

    CANCER RESEARCH   58 ( 10 )   2158 - 2165   1998.5

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  • Mutation, allelotyping, and transcription analyses of the p73 gene in prostatic carcinoma

    H Takahashi, S Ichimiya, Y Nimura, M Watanabe, M Furusato, S Wakui, R Yatani, S Aizawa, A Nakagawara

    CANCER RESEARCH   58 ( 10 )   2076 - 2077   1998.5

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  • 大腸癌におけるp73(p53ホモログ)の遺伝子変異

    砂原 正男, 一宮 慎吾, 宍倉 朋胤, 二村 好憲, 高田 尚幸, 安達 亙, 佐藤 裕二, 天野 純, 藤堂 省, 崎山 樹, 中川 原章

    日本外科学会雑誌   99 ( 0 )   498 - 498   1998.3

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    Language：Japanese   Publisher：一般社団法人日本外科学会  

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  • 食道癌における新規癌抑制遺伝子p73の検討

    二村 好憲, 一宮 慎吾, 砂原 正男, 穴倉 朋胤, 崎山 樹, 関 直彦, 大平 美紀, 藤森 実, 安達 亙, 天野 純, 中川原 章

    日本外科学会雑誌   99 ( 0 )   378 - 378   1998.3

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  • 乳癌における新規p53関連遺伝子p73の検討

    穴倉 朋嵐, 一宮 慎吾, 砂原 正男, 二村 好憲, 宮内 充, 山本 尚人, 鈴木 正人, 中嶋 伸之, 崎山 樹, 中川原 章

    日本外科学会雑誌   99 ( 0 )   339 - 339   1998.3

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  • Ectopic expression of DAN enhances the retinoic acid-induced neuronal differentiation in human neuroblastoma cell lines

    Y Nakamura, T Ozaki, S Ichimiya, A Nakagawara, S Sakiyama

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   243 ( 3 )   722 - 726   1998.2

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  • Localization of rat CD1 transcripts and protein in rat tissues - An analysis of rat CD1 expression by in situ hybridization and immunohistochemistry

    K Kasai, A Matsuura, K Kikuchi, Y Hashimoto, S Ichimiya

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY   109 ( 2 )   317 - 322   1997.8

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    Web of Science

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  • RT1.P, rat class Ib genes related to mouse TL: evidence that CD1 molecules but not authentic TL antigens are expressed by rat thymus

    A Matsuura, S Takayama, M Kinebuchi, Y Hashimoto, K Kasai, D Kozutsumi, S Ichimiya, R Honda, T Natori, K Kikuchi

    IMMUNOGENETICS   46 ( 4 )   293 - 306   1997.8

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  • Rat CD1 antigen: Structure, expression and function

    A Matsuura, Y Hashimoto, M Kinebuchi, K Kasai, S Ichimiya, S Katabami, H Chen, T Shimizu, K Kikuchi

    TRANSPLANTATION PROCEEDINGS   29 ( 3 )   1705 - 1706   1997.5

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  • G-9 GDNFによる神経芽腫の分化誘導およびRet受容体を介するシグナル伝達の解析(神経芽腫(1))

    菱木 知郎, 高橋 英世, 大沼 直躬, 田沼 政裕, 一宮 慎吾, 近藤 和博, 二村 好憲, 尾崎 俊文, 中川原 章

    日本小児外科学会雑誌   33 ( 3 )   542 - 542   1997.5

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    Language：Japanese   Publisher：特定非営利活動法人日本小児外科学会  

    DOI： 10.11164/jjsps.33.3_542_1

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  • Identification and chromosome assignment of a human gene encoding a novel phosphatidylinositol-3 kinase

    Naohiko Seki, Yoshinori Nimura, Miki Ohira, Toshiyuki Saito, Shingo Ichimiya, Nobuo Nomura, Akira Nakagawara

    DNA Research   4   355 - 358   1997.1

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  • Veno-occlusive disease of the liver following bone marrow transplantation: A clinical-pathological study of autopsy cases

    K Watanabe, H Iwaki, M Satoh, T Ikeda, S Ichimiya, N Suzuki, T Kudoh, T Oda, A Matsuura, M Mori, K Kikuchi

    ARTIFICIAL ORGANS   20 ( 10 )   1145 - 1150   1996.10

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    Web of Science

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  • Glial cell-derived neurotrophic factor (GDNF) による神経芽細胞腫の分化誘導とc-Retチロシンキナーゼのシグナル伝達について

    菱木 知郎, 近藤 和博, 二村 好憲, 一宮 慎吾, 崎山 樹, 中川原 章

    神経化学   35 ( 3 )   494 - 495   1996.9

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  • Thioredoxin dependent peroxidase(TPx)のcDNAクローニングとその生物学的意義

    一宮 慎吾, GREENE Mark I, 中川原 章, 崎山 樹

    日本分子生物学会年会プログラム・講演要旨集   19   489 - 489   1996.8

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    CiNii Research

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  • IDENTIFICATION OF THE FUNCTIONAL CLASS-I GENES OF THE RAT BY CDNA CLONING

    R HONDA, A MATSUURA, S TAKAYAMA, S ICHIMIYA, Y ITOH, K KIKUCHI

    TRANSPLANTATION PROCEEDINGS   27 ( 2 )   1515 - 1515   1995.4

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    Web of Science

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  • A MONOCLONAL-ANTIBODY REACTS WITH T-CELLS AND NOVEL SUBPOPULATION OF RAT BONE-MARROW CELLS

    A MATSUURA, M KINEBUCHI, S ICHIMIYA, M SHEN, Y HASHIMOTO, S KATABAMI, K KIKUCHI

    TRANSPLANTATION PROCEEDINGS   27 ( 2 )   1509 - 1510   1995.4

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    Web of Science

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  • STRUCTURAL-ANALYSIS OF THE RAT HOMOLOG OF CD1 - EVIDENCE FOR EVOLUTIONARY CONSERVATION OF THE CD1D CLASS AND WIDESPREAD TRANSCRIPTION BY RAT-CELLS

    S ICHIMIYA, K KIKUCHI, A MATSUURA

    JOURNAL OF IMMUNOLOGY   153 ( 3 )   1112 - 1123   1994.8

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    Web of Science

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  • STRUCTURAL-ANALYSIS OF THE CD3-ZETA-ETA LOCUS OF THE RAT - EXPRESSION OF ZETA BUT NOT ETA-TRANSCRIPTS BY RAT T-CELLS

    Y ITOH, A MATSUURA, M KINEBUCHI, R HONDA, S TAKAYAMA, S ICHIMIYA, S KON, K KIKUCHI

    JOURNAL OF IMMUNOLOGY   151 ( 9 )   4705 - 4717   1993.11

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    Web of Science

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  • MOLECULAR-CLONING OF RAT CLASS-I GENES RELATED TO THE MOUSE TL GENE SUBFAMILY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

    A MATSUURA, S TAKAYAMA, D KOZUTSUMI, S ICHIMIYA, R HONDA, M SHEN, T NATORI, K KIKUCHI

    TRANSPLANTATION PROCEEDINGS   25 ( 5 )   2754 - 2755   1993.10

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    Web of Science

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  • Characterization of Rat CD1 Antigen with a Polyclonal Antibody Against a Recombinant Protein Produced by the Prokaryotic Expression System

    62 ( 4 )   225 - 234   1993.8

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  • ESTABLISHMENT OF APOPTOSIS-INDUCING MONOCLONAL-ANTIBODY 2D1 AND 2D1-RESISTANT VARIANTS OF HUMAN T-CELL LINES

    S TAKAHASHI, N SATO, S TAKAYAMA, S ICHIMIYA, M SATOH, N HYAKUMACHI, K KIKUCHI

    EUROPEAN JOURNAL OF IMMUNOLOGY   23 ( 8 )   1935 - 1941   1993.8

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Awards

  • 科研費審査委員表彰

    2017   日本学術振興会  

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  • 日本病理学会 学術研究賞

    2011  

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  • 日本病理学会カンファレンス 優秀ポスター賞

    2011  

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  • 日本臨床分子形態学会 論文賞

    2005  

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  • 脳腫瘍病理研究会 最優秀論文賞

    2004  

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  • 日本病理学会 学術奨励賞

    2002  

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  • 秋山記念生命科学振興財団 奨励助成

    2001  

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  • 内藤記念科学振興財団 海外留学助成

    1994  

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Research Projects

  • IgG4関連疾患の解析に基づいたヒトIgEのクラススイッチの制御機構の解明

    Grant number：24K12651  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大國 毅, 亀倉 隆太, 一宮 慎吾, 高野 賢一

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • 濾胞ヘルパーT細胞の病理組織環境における機能動態の解明

    Grant number：23H02695  2023.4 - 2027.3

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    一宮 慎吾

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    Grant amount：\18720000 （ Direct Cost: \14400000 、 Indirect Cost：\4320000 ）

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  • T 細胞疲弊を標的としたアレルギー性鼻炎の新規治療戦略

    Grant number：22K09670  2022.4 - 2026.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    山本 圭佑, 一宮 慎吾, 高野 賢一, 亀倉 隆太

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

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  • T 細胞老化に関連した慢性炎症性疾患の発症メカニズムの解明

    Grant number：21K09658  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    亀倉 隆太, 一宮 慎吾, 高野 賢一

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    IgG4関連疾患(IgG4-RD)の病因としてIgG4産生に関わる適応免疫系の機能異常が存在すると考えられているが、未だ病態の全容解明には至っていない。IgG4-RDの病変部位には多数のCD4陽性T細胞の浸潤が認められ、また一方で難治性免疫関連疾患の病態背景にエフェクターヘルパーCD4陽性T細胞が関与することから、我々はCD4陽性T細胞サブセットの一つである末梢ヘルパーT(Tph)細胞に注目してIgG4-RDの病態解析を行っている。CXCR5などのケモカインレセプターの発現パターンからTph細胞は病変部位(リンパ濾胞外)で機能を発揮すると考えられており、特定のB細胞サブセットとの相互作用が推察される。今回我々はTph細胞の制御機構を明らかにするために、濾胞外B細胞(CD19+CD11c+CD21-)に着目して、IgG4-RDにおける濾胞外B細胞の機能的役割やTph細胞との相互作用について検討した。結果、IgG4-RD患者では健常者と比較して血液濾胞外B細胞の割合が増加していた。また血液Tph細胞の割合と濾胞外B細胞の割合との間に有意な正の相関関係を認めた。一方血液濾胞ヘルパーT(Tfh)細胞の割合と濾胞外B細胞の割合との間には相関関係を認めなかった。この結果から、Toll-like receptorを発現する濾胞外B細胞が抗原提示細胞としてTph細胞の分化・増殖に関与している一方で、Tph細胞が抗体産生などの濾胞外B細胞の機能を制御している可能性が考えられた。このTph細胞と濾胞外B細胞との関係は適応免疫と自然免疫のクロストークの一例といえる。Tph細胞はIgG4-RDにとどまらず、他の慢性炎症性疾患の病態形成に関与している可能性があることから、今後も検討を進めていきたい。

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  • 唾液腺免疫性疾患における腺機能障害に対する基礎的研究

    Grant number：21K09610  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    高野 賢一, 小島 隆, 一宮 慎吾, 亀倉 隆太

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    すでに確立しているヒト唾液腺腺管上皮細胞の培養系を用いて、タイト結合分子の中でも特にcutokinesisにおけるlipolysis-stimulated lipoprotein receptor (LSR)およびtricellulinに着目した。現在のところ、
    2細胞間タイト結合分子であるoccludin, claudin-7, zonula occludens-1 cingulinや極性に関与するPAR3が、cytokinesisにおいて発現増強し、上皮バリア機能も保たれ、LSRやtricellulin がアセチル化チューブリン陽性中央体やガンマチューブリン陽性中心体にHook2とともに認められた。Hook2をノックダウンすると上皮バリア機能低下や関連分子の発現が中心体から消失した。LSRの多様な機能が示唆されている。

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  • Study of functional characteristics of cytotoxic Tfh cells and their pathological significance

    Grant number：18H02632  2018 - 2022

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Ichimiya Shingo

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    Authorship：Principal investigator  Grant type：Competitive

    This study aimed to characterize the functional features of T follicular helper cells (Tfh cells) in ectopic lymphoid tissues with chronic inflammation. The analysis of fibroinflammatory lesions of IgG4-related disease (IgG4-RD) revealed that the Tfh cell population contained double-positive Tfh cells (DP-Tfh cells), which expressed both CD4 and CD8 and presented cytotoxicity-related molecules, including Eomes, granzymes, perforin, CRTAM, and GPR56. Studies of clinical parameters and co-culture experiments using autologous T and B cells suggest that DP-Tfh cells would regulate memory B cells. Further in vitro experiments showed that normal Tfh cells could differentiate into DP-Tfh cells under the stimulation with IL-2 and IL-7, which was highly expressed in the tissue lesions of IgG4-RD. Taken together, DP-Tfh cells may play a possible role in inhibiting memory B cell function to control the antibody production program within a persistent inflammatory environment.

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  • The mechanisms of salivary gland fibrosis in IgG4-related disease

    Grant number：18K09324  2018 - 2020

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Takano Kenichi

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    Grant type：Competitive

    The aim of this study was to investigate the mechanisms driving fibrosis in the submandibular glands (SMG) of patients with IgG4-related disease (IgG4-RD). Our results suggest fibrosis in the SMG of affected patients is closely linked to the proliferation of fibroblasts following induction of IL-6 and WISP1 by inflammatory cytokines. The Th2 cytokines TSLP and IL-33 are also upregulated in affected SMG, and thus may cause chronic inflammation and IgG4 accumulation.

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  • 濾胞ヘルパーT細胞の新たなサブセットによる自己免疫病態の形成

    2017

    ブリストル・マイヤーズ スクイブ  研究助成（免疫領域） 

    一宮慎吾

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    Authorship：Principal investigator  Grant type：Competitive

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  • Analysis of humoral abnormality caused by functional imbalance of follicular helper T cells.

    Grant number：16K15723  2016.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Himi Tetsuo

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    Grant amount：\3510000 （ Direct Cost: \2700000 、 Indirect Cost：\810000 ）

    To determine the pathophysiologic features of diseases regarding immunological dysregulation, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood and affected lesion from allergic rhinitis (AR) and IgG4-RD patients. The results showed skewed polarization of Tfh cell subsets in both AR and IgG4-RD cases. Interestingly, the %Breg cells in total B cells were decreased in AR cases and, more extensively, in AR. Moreover, we found significant correlations of fractional exhaled nitric oxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that relative decrease in Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing PD-1 and ICOS in submandibular glands.

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  • New treatment strategy for allergic diseases by targeting blood type 2 follicular helper T cells and regulatory B cells

    Grant number：15K10787  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Kamekura Ryuta, ICHIMIYA Shingo, HIMI Tetsuo

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

    We analyzed lymphocytes in blood from patients with birch pollen allergy. The percentage of circulating Tfh2 cells in blood from patients with birch pollen allergy during the non-pollen season was increased compared with that in blood from healthy volunteers. We also found that the percentage of ICOS+ Tfh cells in blood from patients with birch pollen allergy increased during the pollen season and decreased during the non-pollen season. The percentage of circulating ICOS+ Tfh cells in blood from patients with birch pollen allergy was positively correlated with total symptom scores and level of birch-specific serum IgE. In addition, an increase in Bet v1-specific MHC class 2 tetramer-positive and ICOS+ Tfh cells was seen in patients with birch pollen allergy during the pollen season. The results suggest that elevated circulating Tfh2 cells reflect an allergic predisposition and that birch-specific and ICOS+ Tfh cells play an important role in the pathogenesis of birch pollen allergy.

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  • The relationship between follicular helper T cells and pathogenesis of tonsillar hypertrophy in patients with child OSAS

    Grant number：15K20213  2015 - 2016

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    Tsubomatsu Chieko, HIMI Tetsuo, ICHIMIYA Shingo, KAMEKURA Ryuta, NAGAYA Tomonori, YAMASHITA Keiji, SHINTANI Tomoko, Ito Fumie

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    Grant type：Competitive

    Obstructive sleep apnea syndrome (OSAS) in childhood is caused by adeno-tonsillar hypertrophy, and adeno-tonsillectomy is commonly performed as a treatment.Histologically, tonsillar hypertrophy is characterized by prominent germinal centers (GCs). Antigen specific humoral immune responses are established by the active interactions of B and Tfh cells (follicular helper T cells) in GCs. Therefore, we focused on the potential of these cells to induce lymphoid hyperplasia promoted in OSAS pathogenesis. The results revealed that the tonsils of OSAS were considerably different from those of RT tonsils in terms of Tfh cells. Moreover, lipoxin A4 and leukotriene B4 have the capacity to differentiate naive CD4+ T cells into Tfh cells. The results suggest that such lipid mediators have a potential role in the development of lymphoid follicles through the regulation of Tfh cell differentiation and regulation of these mediators should be considered as a candidate of conservative treatment.

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  • Development of immunopathologic diagnosis with a new transition marker of follicular helper T cells

    Grant number：26670178  2014 - 2015

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Ichimiya Shingo, HIMI Tetsuo, SATO Noriyuki, KAWATA Koji, KAMEKURA Rhyuta

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    Authorship：Principal investigator  Grant type：Competitive

    In this study, we performed functional analysis of T follicular helper (Tfh) cells and their transitional cell subsets to apply novel findings for histopathological examinations of immune-related disorders. As a result, we found high expression of a Bob1 transcription factor in Tfh cells and the involvement of Bob1 in the regulation of cell numbers of Tfh cells (Eur J Immunol. 2016). Further, we revealed that Tfh2-cell polarization preferentially occurred in the patients with allergic asthma and allergic rhinitis, as seen as Th2-cell polarization in the patients（Clin Immunol. 2015）. This implies the common mechanism underlying Tfh2-cell and Th2-cell polarization, suggesting that a manner of skewing of Tfh-cell subset would reflect a disease-specific feature of helper CD4(+) T cells. By virtue of a characteristic molecule(s) in Tfh cells and Tfh-cell subsets, further studies might lead to a new modality for histopathological diagnosis of immune-related disorders.

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  • Analysis of antibody production program underlying immune-related disorders of human system

    Grant number：23590405  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ICHIMIYA Shingo, HIMI Tetsuo, SATO Noriyuki

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    Authorship：Principal investigator  Grant type：Competitive

    Follicular helper T (Tfh) cells play a cardinal role in the production of high-affinity antibodies and their plasticity enables to become other effector helper T cells; however, regulatory mechanism of human Tfh cells is not fully elucidated. In this study we aimed to understand biomedical features of human Tfh cells. Results demonstrated that hypertrophic tonsils of the patients with obstructive sleep apnea syndrome preferentially possessed Tfh cells within enlarged lymphoid follicles. When examined blood Tfh cells of patients with immune-related disorders including allergic rhinitis or asthma, Tfh2 cells were predominantly observed. Thus far unusual manner of Tfh cell differentiation (named Tfh-shift or Tfh2-shift in this study) would be attributable for underlying conditions of such disorders. Further studies should be required, although ALOX5-related lipid mediators and/or POU2AF1 might be involved in the skewed differentiation of human Tfh cells.

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  • Molecular immunopathology of human cancer stem cell

    Grant number：21249025  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    SATO Noriyuki, TORIGOE Toshihiko, ICHIMIYA Shingo, TAMURA Yasuaki, HIROHASHI Yoshihiko, KIKUCHI Tomoki

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    Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type：Competitive

    This study was aimed to analyze molecular pathological nature of human cancer stem cell(CSC)/cancer-initiating cell(CIC). Particularly we studied molecules expressed specifically in CSC/CIC and their immunological characteristics. Consequently we successfully identified such interesting antigens. These antigens have molecular features of cancer-testis antigens, and could work as potential immunogenic molecule in human cancers.

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  • Novel role of ALOX5 (L22) in the control of antibody production

    Grant number：20590347  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ICHIMIYA Shingo

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    Authorship：Principal investigator  Grant type：Competitive

    We have previously reported L22 mAb with which human primary resting B cells and other immune cells of lymphoid follicles are well defined. In this study, we first identifiedL22 Ag as arachidonate 5-lipoxyganase (Alox5) and our experimental results illustrated the novel role of Alox5 during the process of specific antibody production by managing naive and memory B cells as well as follicular helper T cells in vivo. Because Alox5 is a key enzyme giving lipid mediators like leukotrienes, further investigations focusing on metabolome may provide new insights into the mechanisms of innate and adaptive immune responses and the pathogenesis of allergic and chronic inflammatory disorders (Nagashima T, et al. American Journal of Pathology, 2011).

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  • Analysis of relationship in immune barrier function between human nasal epithelial cell and dendritic cell.

    Grant number：19390436  2007 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    HIMI Tetsuo, KOJIMA Takashi, GO Mitsuru, ICHIMIYA Shingo, TAKANO Ken-ichi

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    Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type：Competitive

    Analysis of a immune barrier function with primary culture system of human nasal mucosa epithelium is important to establish a methodology of inflammation control by trans-nasal administration. Tight junction is one of an important factor contributing to permeability of a material, and it is important to study a factor regulating this function. Furthermore, examination of immunocompetent cell about an antigen sampling such as dendritic cell contributes to establish the mechanism of immune therapy for allergic rhinitis or upper respiratory infection by trans-nasal administration.

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  • Analysis of pathogenesis of obliterative bronchiolitis using gene expression profiling

    Grant number：19591490  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    MORIKAWA Masayuki, ICHIMIYA Shingo

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    Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type：Competitive

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  • Immune response and escape in human cancers

    Grant number：16209013  2004 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    SATO Noriyuki, TORIGOE Toshihiko, ICHIMIYA Shingo, SAHARA Hiroeki, TAMURA Yasuaki, KAMIGUCHI Kenjiro

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    Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type：Competitive

    The investigation of human tumor immunotherapy has remarkably advanced in the past decade. In our laboratory, human tumor antigens and their HLA-A24-restricted immunogenic peptide epitopes were determined to develop therapeutic and prophylactic human cancer vaccines. Among these peptides, survivin 2B peptide derived from survivin, an inhibitor of apoptosis protein (IAP), is immunogenic in more than 50 % of cancer patients with a wide variety of tumors, including colon, pancreas, lung, breast, urinary bladder and oral cancers. It is now under clinical and with careful immunological monitoring we will finally be able to know if these vaccines can work clinically.
    To develop a potent clinical therapeutic protocol, the immunological tumor escape mechanism should be more thoroughly examined in human tumor materials. To this end, anti-HLA-A, B, and C allele-specific monoclonal antibody EMR8-5, which can be used in routine paraffin-embedded sections, was successfully established. Unexpectedly, our data indicated that a high percentage of human cancers, particularly breast and prostate cancers, lost HLA-class I molecules in their primary cancer tissues. We will discuss possibilities for resolution of this important old but yet new problem.
    Although recent evidence has been accumulating for an important role of the heat shock proteins (HSPs) as so-called danger signals in initiating innate immunity and consequently activating acquired immunity, the precise immunological basis for this phenomenon remains to be elucidated. Our study indicated that certain HSP-chaperoned immunogenic peptides, particularly HSP90, could efficiently enter the cross-priming pathway in dendritic cells. Interestingly, this cross-priming was TAP-independent and followed endocytic pathways. We also showed that HSP90-chaperoned peptide complexes could work as a potential tumor therapeutic vaccine in the HLA-A24 transgenic mouse model.

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  • Roles of heterogeneity of thymic medullary epithelial cells in the regulation of human immune response

    Grant number：16590286  2004 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ICHIMIYA Shingo

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    Authorship：Principal investigator  Grant type：Competitive

    Regulatory mechanisms of stromal cells localized in the medullary regions are mostly unknown, which are actively involved in the purging process of self-reactive T cells to avoid immune-related disorders such as allergic and autoimmune diseases. In this program, we first discovered roles of p63 and p73 of p53-related transcription factors acting as ‘a new functional marker' of medullary epithelial cells (MECs) of the human thymus and a part of them showed heterogeneous expression of p63 and p73 in their nuclei. Focusing on these findings of MECs, we also found that autoimmune regulator (AIRE), whose mutations lead to autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), had the capacity to form a complex with p63, but not p73. Interestingly, p53, p63 and p73 could solely downregulate the expression of HLA-II, whereas AIRE/p63 did not have such an activity. Together with the evidence that G228W mutation of AIRE could not bind to the AIRE-associated domain of p63, an AIRE/p63 complex in MECs might modulate the expression of HLA-II by quenching the suppressive activities of p63 to keep away from possible leakage of self-reactive CD4 T cells from the thymus. Selection events of self-reactive T cells are provided by scaffolding network of medullary stromal cells including epithelial cells and dendritic cells, which were found to be connected with junctional complex by immunohistochamical and freeze-fracture replica analyses. More interestingly, our data employing microinjection methods suggested that small molecules could be transferred form a MEC to he next ones. Thus far short peptides derived from self-antigens would be shared by MECs.

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  • Cell Growth Control by Regulating the Expression of p73 : the Basics and Development of New Clinical Applications

    Grant number：13670182  2001 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ICHIMIYA Shingo, SATO Noriyuki

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    Authorship：Principal investigator  Grant type：Competitive

    Accumulating evidence has demonstrated that the gene encoding p73, a molecule homologous to the archetypal tumor suppressor p53, knows infrequent mutation in various human malignancies unlike p53. Together with functional similarities of p73 to p53, we hypothesized that tumor cell growth might be controlled when an intrinsic p73 of tumor cells could be up-regulated by hitherto unknown mechanism. To elucidate the mechanism, we have newly made antibodies specific to p73 and analyzed a series of human tissues. Results indicated that p73 was specifically localized at the nuclei of thymic medullary epithelial cells, but not in cortical epithelium. Moreover, in vitro studies using thymic epithelial cell lines showed that p73 was potentially involved regulation of M-CSF as well as GM-CSF. It is well known that in medullary epithelium foster dendritic cells and macrophages for establishing negative selection of immature T cells in the region. Thus, these imply that p73 in the medulla might have important roles, to control stromal cells for negative selection. We also investigated a. molecule specifically regulating the expression of p73 from biologically active molecules of natural resources in collaboration with the Institute of Marine Bioscience of our university. Currently, we have found a. certain fraction of the Aristertoles of. sea urchin has a capacity to up-regulating p73 of human thymic epithelial cells. We would like to further clarify the expression mechanism of p73 and develop its related methodology for controlling tumor cell cycle as well as tumor immunity possibly through the activation of antigen presenting cells.

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  • リンパ増殖性疾患におけるp73の機能解析

    Grant number：12215125  2000

    文部科学省  特定領域研究(C)  特定領域研究(C)

    一宮慎吾, 佐藤 昌明, 佐藤 昇志

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    Authorship：Principal investigator  Grant type：Competitive

    (目的)
    リンパ増殖性疾患におけるp73の発現を検索するため、p73アイソフォームの中で最も発現が高いp73αに対する抗体を作成し、免疫組織化学的検討とともに分子生物学的解析を行った。
    (方法)
    リンパ節や胸腺といった正常組織とともに、様々な種類の悪性リンパ腫や胸腺腫を対象として免疫組織化学を行った。また、p73αのcDNAをプローブとしたノザン解析により遺伝子発現も検討した。
    (結果と考察)
    1.正常のリンパ節や脾臓、胸腺皮質を用いた結果、各分化段階のT細胞、B細胞いずれにおいても、p73αの発現は免疫組織化学の検出感度以下であった。また検索した範囲では、各種悪性リンパ腫でのp73αの発現異常も見られなかった。一方、遺伝子再構成を余儀なくされるリンパ球の分化過程において、oncogenic translocationを抑制する機構が明らかにされつつある。DNA修復依存性の細胞死に深く関係しているp73が、RT-PCR法によりリンパ球に発現していることが報告されており、この機構にp73が関与しているかどうかは今後検討すべき課題と思われる。
    2.胸腺組織ではリンパ球に発現が見られなかったが、胸腺上皮細胞の細胞核に発現が認められた。ノザン解析でも胸腺組織でのp73α遺伝子の発現が観察された。リンパ増殖性疾患の中で、悪性リンパ腫にはp73αの発現異常は確認されたかったものの、様々な程度でリンパ球増殖を伴っている胸腺腫においてp73αの発現が低下していた。このことは、転写因子として機能するp73αの発現異常が胸腺腫発生に関与する可能性を示唆する。また、T細胞と胸腺上皮細胞との関係は、胸腺腫のみならず、自己免疫疾患などT細胞の機能異常が関与する疾病とも連関しており、p73に視点を置いた両者の関係が明らかにされれば、免疫異常の研究にも大きな展開がもたらされるかもしれない。

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  • 膀胱癌のCarcinoma in situ(CIS)における遺伝子異常

    Grant number：11770123  1999 - 2000

    日本学術振興会  奨励研究(A)  奨励研究(A)

    一宮慎吾

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    Authorship：Principal investigator  Grant type：Competitive

    (目的)膀胱癌のCISにおける遺伝子的変異を検索することを目的として、現在までに知られている代表的分子種のcDNAを含むcDNA arrayを用い解析を行った。
    (方法)単一細胞からcDNA libraryを作成するプロトコールを参照し(Dulac C.、Current Topics of Developmental Biology、36、1998)、トリミングした新鮮凍結切片からcDNAを作成した。これらをアイソトープで標識し、cDNA array blotとハイブリダイゼーションを行った。CIS病変ならび対照としての正常粘膜には、術中迅速診断で用いた尿管断端の凍結切片を用いた。免疫組織化学については、パラフィン切片を用いて通常行われている方法で検討した。
    (結果と考案)CISおよび正常粘膜をプローブとしたオートラジオグラフィーのフィルムを比較検討した結果、CISにおいてintegrin beta 3の発現が低下していた。免疫組織化学的検討にても、integrin beta 3の発現に差が認められ、p53陽性細胞とほぼ一致してその発現が低下していた。正常粘膜ではintegrin beta 3は傘細胞に発現が強い傾向があった。PCR法で得られたcDNAをプローブとして用いているため、バイアスがかかることが予想されたが、cDNA arrayによる検索は、微細な病変の遺伝子解析に有用であると考えられた。今後は、integrin beta3のdown-regulationが腫瘍化に際しどのように関与しているのか、またp53ファミリーに属するp73との関係についても検討してゆきたい。
    ※今回の研究成果の一部は、平成12年4月の第89回日本病理学会総会で発表された。

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Teaching Experience

  • 免疫学（総論、各論）

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  • 病理学（総論、各論）

    Institution：札幌医科大学

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