ICHIMIYA Shingo

写真a

Affiliation

Institute of Immunology, Department of Human Immunology

Job title

Professor

Homepage URL

http://web.sapmed.ac.jp/immunology/index.html

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Education 【 display / non-display 】

  • 1990
    -
    1994

    Sapporo Medical University   Graduate School of Medicine   博士課程病理系 修了  

  • 1984
    -
    1990

    Sapporo Medical University   School of Medicine   卒業  

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Degree 【 display / non-display 】

  • 札幌医科大学   MD (1990)、PhD (Medical Science 1994)

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Research Experience 【 display / non-display 】

  • 2021.04
    -
    2022.03

    Sapporo Medical University   Research Institute for Frontier Medicine   所長

  • 2020.04
    -
    2022.03

    札幌医科大学   動物実験施設部   部長

  • 2018.04
    -
    2022.03

    Sapporo Medical University   医学部カリキュラム委員会   委員長

  • 2013.05
    -
    Now

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

  • 2010.10
    -
    2013.04

    Sapporo Medical University   School of Health Sciences   Professor

    Professor

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Professional Memberships 【 display / non-display 】

  • 　
    　
    　

    米国免疫学会（AAI）

  • 　
    　
    　

    THE JAPANESE SOCIETY OF PATHOLOGY

  • 　
    　
    　

    日本分子生物学会

  • 　
    　
    　

    日本癌学会

  • 　
    　
    　

    日本免疫学会

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Research Areas 【 display / non-display 】

  • Life sciences   Laboratory animal science  

  • Life sciences   Immunology  

  • Life sciences   Human pathology  

  • Life sciences   Experimental pathology  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   Research Institute for Frontier Medicine   Professor  

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Research Interests 【 display / non-display 】

  • immune related disorders

  • immune tissues

  • immune cells

  • human immune system

  • follicular helper T cell

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Papers 【 display / non-display 】

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

    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  2024.02  [International journal]

    　View Summary

    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 PubMed

  • 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 ( Frontiers Media SA )  14  2023.11

    　View Summary

    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+ cTfh cells were significantly decreased and the percentage of IFN-γ+ 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

  • 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 ( (一社)日本アレルギー学会 )  72 ( 6-7 ) 872 - 872  2023.08

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

    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  2023.02  [International journal]

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    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 PubMed

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

    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  [International journal]

    　View Summary

    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 PubMed

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Misc 【 display / non-display 】

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Awards 【 display / non-display 】

  • 科研費審査委員表彰

    2017   日本学術振興会  

  • 日本病理学会カンファレンス 優秀ポスター賞

    2011  

  • 日本病理学会 学術研究賞

    2011  

  • 日本臨床分子形態学会 論文賞

    2005  

  • 脳腫瘍病理研究会 最優秀論文賞

    2004  

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Research Projects 【 display / non-display 】

  • 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

    基盤研究(B)

    Project Year :

    2023.04
    -
    2027.03
     

    一宮 慎吾

  • 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

    基盤研究(C)

    Project Year :

    2022.04
    -
    2026.03
     

    山本 圭佑, 一宮 慎吾, 高野 賢一, 亀倉 隆太

  • 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

    基盤研究(C)

    Project Year :

    2021.04
    -
    2024.03
     

    高野 賢一, 小島 隆, 一宮 慎吾, 亀倉 隆太

    　View Summary

    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。

  • 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

    基盤研究(C)

    Project Year :

    2021.04
    -
    2024.03
     

    亀倉 隆太, 一宮 慎吾, 高野 賢一

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    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。

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

    Grant-in-Aid for Scientific Research (B)

    Project Year :

    2018
    -
    2022
     

    Ichimiya Shingo

    Authorship： Principal investigator

    　View Summary

    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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Teaching Experience 【 display / non-display 】

  • 病理学（総論、各論）  

    札幌医科大学  

  • 免疫学（総論、各論）  

    札幌医科大学、関西学院大学  

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Committee Memberships 【 display / non-display 】

  • 2014
    -
    Now

      評議員

  • 2002
    -
    Now

      学術評議員

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