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Inhibitory cytokine-producing Treg-mediated control of autoimmunity

Research Project

Project/Area Number 16K15510
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionThe University of Tokyo

Principal Investigator

Fujio Keishi  東京大学, 医学部附属病院, 教授 (70401114)

Research Collaborator KOMAI TOSHIHIKO  東京大学, 医学部附属病院, 特任臨床医 (50803938)
INOUE MARIKO  東京大学, 医学部附属病院, 特任臨床医 (60816601)
MORITA KAORU  東京大学, 医学部附属病院, 特任臨床医
TERUYA SHUZO  東京大学, 医学部附属病院, 特任臨床医
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords制御性T細胞 / TGF-β / LAG3 / TGF-β3 / IL-10 / TGF-beta3 / Egr2 / サイトカイン / TGF-beta / ノックアウトマウス
Outline of Final Research Achievements

The aim of this project was to elucidate the role of inhibitory cytokine in regulatory T cell (Treg)-mediated control of autoimmunity. Although inhibitory cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) play major roles in maintaining immune homeostasis, therapeutic application of inhibitory cytokines remains limited due to their pleiotropic and context-dependent effects. In this study, we reveled that a combination of TGF-β and IL-10, but not single cytokine, is required to suppress B cell activation induced by toll-like receptor (TLR) stimulation both in vitro and in vivo. The combination of these two inhibitory cytokines synergistically suppressed cellular energetics of both glycolysis and oxidative phosphorylation in B cells. By exploiting the cytokine synergy-mediated immune suppression, they may provide a new therapeutic method in autoantibody-mediated autoimmune diseases.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 Other

All Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Early Growth Response Gene 2-Expressing CD4+LAG3+ Regulatory T Cells: The Therapeutic Potential for Treating Autoimmune Diseases2018

    • Author(s)
      Okamura Tomohisa、Yamamoto Kazuhiko、Fujio Keishi
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 1-9

    • DOI

      10.3389/fimmu.2018.00340

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overview of LAG-3-Expressing, IL-10-Producing Regulatory T Cells2017

    • Author(s)
      Fujio Keishi、Yamamoto Kazuhiko、Okamura Tomohisa
    • Journal Title

      Curr Top Microbiol Immunol

      Volume: 410 Pages: 29-45

    • DOI

      10.1007/82_2017_59

    • ISBN
      9783319689289, 9783319689296
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The metabolic regulation in immune cells and pathogenesis of systemic lupus erythematosus ∼toward new therapeutic applications∼2017

    • Author(s)
      竹島 雄介、岩崎 由希子、岡村 僚久、藤尾 圭志、山本 一彦
    • Journal Title

      Japanese Journal of Clinical Immunology

      Volume: 40 Issue: 1 Pages: 12-20

    • DOI

      10.2177/jsci.40.12

    • NAID

      130005665586

    • ISSN
      0911-4300, 1349-7413
    • Related Report
      2017 Annual Research Report
  • [Journal Article] Interleukin-10-producing LAG3+ regulatory T cells are associated with disease activity and abatacept treatment in rheumatoid arthritis2017

    • Author(s)
      Nakachi Shinichiro、Sumitomo Shuji、Tsuchida Yumi、Tsuchiya Haruka、Kono Masanori、Kato Rika、Sakurai Keiichi、Hanata Norio、Nagafuchi Yasuo、Tateishi Shoko、Kanda Hiroko、Okamura Tomohisa、Yamamoto Kazuhiko、Fujio Keishi
    • Journal Title

      Arthritis Research & Therapy

      Volume: 19 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s13075-017-1309-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of tonsillar CD4±CD25=LAG3± T cells as naturally occurring IL-10-producing regulatory T cells in human lymphoid tissue.2017

    • Author(s)
      Sumitomo S, Nakachi S, Okamura T, Tsuchida Y, Kato R, Shoda H, Furukawa A, Kitahara N, Kondo K, Yamasoba T, Yamamoto K, Fujio K.
    • Journal Title

      Journal of autoimmunity.

      Volume: 76 Pages: 75-84

    • DOI

      10.1016/j.jaut.2016.09.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transforming Growth Factor-β3 Inhibits Antibody Production by Human B Cells.2017

    • Author(s)
      Tsuchida Y, Sumitomo S, Ishigaki K, Suzuki A, Kochi Y, Okamura T, Yamamoto K, Fujio K.
    • Journal Title

      PLoS One

      Volume: 12 Issue: 1 Pages: 1-16

    • DOI

      10.1371/journal.pone.0169646

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The effects of TGF-βs on immune responses2016

    • Author(s)
      Fujio K, Komai T, Inoue M, Morita K, Okamura T, Yamamoto K.
    • Journal Title

      Japanese Journal of Clinical Immunology

      Volume: 39 Issue: 1 Pages: 51-58

    • DOI

      10.2177/jsci.39.51

    • NAID

      130005151098

    • ISSN
      0911-4300, 1349-7413
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of regulatory cytokines that target B cells.2016

    • Author(s)
      Fujio Keishi, Okamura Tomohisa, Sumitomo Shuji, Yamamoto Kazuhiko
    • Journal Title

      Internal Immunology

      Volume: 28 Issue: 4 Pages: 189-195

    • DOI

      10.1093/intimm/dxv069

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerging roles of Egr2 and Egr3 in the control of systemic autoimmunity.2016

    • Author(s)
      Morita K, Okamura T, Sumitomo S, Iwasaki Y, Fujio K, Yamamoto K.
    • Journal Title

      Rheumatology (Oxford)

      Volume: 55(suppl 2) Issue: suppl 2 Pages: 76-81

    • DOI

      10.1093/rheumatology/kew342

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] A landscape of autoimmune diseases from multisubset transcriptome analysis2017

    • Author(s)
      Keishi Fujio
    • Organizer
      4th Symposium on Max Planck-The University of Tokyo Center for Integrative
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CD4陽性T細胞における転写因子Klf1を介したPD-L1発現誘導機構2017

    • Author(s)
      照屋周造、岡村僚久、竹島雄介、駒井俊彦、井上真璃子、岩崎由希子、山本一彦、藤尾圭志
    • Organizer
      第45回日本臨床免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] B細胞を抑制するCD4陽性CD25陰性LAG3陽性制御性T細胞2016

    • Author(s)
      藤尾圭志、岡村僚久、駒井俊彦、井上眞璃子、森田薫、住友秀次、山本一彦
    • Organizer
      第60回 日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] TGF-β3およびIL-10による協調性液性免疫制御機構の解明2016

    • Author(s)
      井上眞璃子、岡村僚久、駒井俊彦、森田薫、照屋周造、岩崎由希子、住友秀次、山本一彦、藤尾圭志
    • Organizer
      第60回 日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Remarks] 東京大学医学部附属病院 アレルギーリウマチ内科

    • URL

      http://ryumachi.umin.jp/about/research.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学医学部附属病院 アレルギーリウマチ内科 第18研究室

    • URL

      http://plaza.umin.ac.jp/areriu18/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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