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Elucidation of suppressive mechanisms of autoreactive B cells byCD4+CD25-LAG3+ regulatory T cells

Research Project

Project/Area Number 23791106
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionThe University of Tokyo

Principal Investigator

OKAMURA Tomohisa  東京大学, 医学部附属病院, 特任助教 (10528996)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords制御性T細胞 / 自己抗体 / 全身性エリテマトーデス / LAG3 / Egr2
Research Abstract

The aim of this project is to elucidate the role of Egr2-expressing CD4+CD25-LAG3+ regulatory T cells (LAG3 Treg) in regulation of autoantibody production. Adoptive transfer of LAG3 Treg from control MRL/+ mice to MRL/Faslpr lupus prone mice significantly suppressed the progression of nephritis and autoantibody production. Interestingly, LAG3 Treg co-expressed Egr2 and PD-L1, and LAG3 Treg from T-cell-specific Egr2 conditional knockout or PD1 knockout mice failed to suppress B cell antibody production. These findings elucidate that LAG3 Treg play a crucial role in preventing the excessive B cell responses via Fas/FasL and PD-1/PD-L1 interactions. By exploiting the capacity of LAG3+ Tregs, they may provide a new therapeutic method in autoantibody-mediated autoimmune diseases, including SLE.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (21 results)

All 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 8 results) Presentation (8 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Toward therapeutic application of IL-10-producing regulatory T cells2013

    • Author(s)
      Iwasaki Y, Fujio K, Okamura T, Yanai A, Yamamoto K
    • Journal Title

      Jpn J Clin Immunol

      Volume: 36(1) Pages: 40-6

    • Related Report
      2012 Final Research Report
  • [Journal Article] Egr2 and Egr3 are the unique regulators for systemic autoimmunity2013

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

      JAK-STAT

      Volume: 2:2

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells2013

    • Author(s)
      Iwasaki, Y.
    • Journal Title

      Eur J Immunol

      Volume: undefined Issue: 4 Pages: 1063-73

    • DOI

      10.1002/eji.201242942

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory cell subsets in the control of autoantibody production related to systemic autoimmunity.2013

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

      Ann Rheum Dis

      Volume: 72 Pages: 1-8

    • DOI

      10.1136/annrheumdis-2012-202341

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Egr2 and Egr3 are the unique regulators for systemic autoimmunity.2013

    • Author(s)
      Shuji Sumitomo
    • Journal Title

      JAK-STAT

      Volume: 2 Pages: 1-3

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Toward therapeutic application of IL-10-producing regulatory T cells.2013

    • Author(s)
      Yukiko Iwasaki
    • Journal Title

      Jpn J Clin Immunol

      Volume: 36 Pages: 40-46

    • Related Report
      2012 Annual Research Report
  • [Journal Article]2012

    • Author(s)
      Izawa S, Okamura T, Matsuzawa K, Ohkura T, Ohkura H, Ishiguro K, Noh JY, Kamijo K, Yoshida A, Shigemasa C, Kato M, Yamamoto K, Taniguchi SI
    • Journal Title

      Clin Endocrinol (Oxf)

      Volume: 79 Issue: 1 Pages: 35-42

    • DOI

      10.1111/cen.12121

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Roles of LAG3 and EGR2 in regulatory T cells.2012

    • Author(s)
      Tomohisa Okamura
    • Journal Title

      Ann Rheum Dis

      Volume: 71 Pages: 96-100

    • DOI

      10.1136/annrheumdis-2011-200588

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of autoantibodies to citrullinated BiP in rheumatoid arthritis patients and pro-inflammatory role of citrullinated BiP in collagen-induced arthritis2011

    • Author(s)
      Shoda H, Fujio K, Shibuya M, Okamura T, Sumitomo S, Okamoto A, Sawada T, et al.
    • Journal Title

      Arthritis Res Ther

      Volume: 13 Issue: 6 Pages: 1-12

    • DOI

      10.1186/ar3520

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulatory T-cell-associated cytokines in systemic lupus erythematosus2011

    • Author(s)
      Okamoto A, Fujio K, Okamura T, Yamamoto K
    • Journal Title

      J Biomed Biotechnol

      Volume: 2011 Issue: 1 Pages: 463412-463412

    • DOI

      10.1155/2011/463412

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] CD4+CD25-LAG3+ regulatory T cell controls B cell activation via PD-1/PD-L1 and Fas/FasL interactions2013

    • Author(s)
      Tomohisa Okamura
    • Organizer
      The 5th GlobalCOE Retreat (Global Center of Education and Research for Chemical Biology of the Disease)
    • Place of Presentation
      Oiso Grand Hotel, Kanagawa
    • Related Report
      2012 Final Research Report
  • [Presentation] “CD4+CD25-LAG3+ regulatory T cell controls B cell activation via PD-1/PD-L1 and Fas/FasL interactions.”2013

    • Author(s)
      Tomohisa Okamura
    • Organizer
      The 5rd Global COE Retreat (Global Center of Education and Research for Chemical Biology of the Disease)
    • Place of Presentation
      大磯グランドホテル, 神奈川県
    • Related Report
      2012 Annual Research Report
  • [Presentation] DEVELOPMENT OF AUTOANTIBODY SUPPRESSIVE EGR2 EXPRESSING CD4+CD25-LAG3+ REGULATORY T CELLS ISDEPENDENT ON FAS-FAS LIGAND INTERACTION2012

    • Author(s)
      Tomohisa Okamura
    • Organizer
      8th International Congress on Autoimmunity 2012
    • Place of Presentation
      Congress, Granada, Spain on
    • Year and Date
      2012-05-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Fas-FasL dependent induction of autoantibody suppressive Egr2 expressing CD4+CD25-LAG3+ regulatory T cell2012

    • Author(s)
      Tomohisa Okamura
    • Organizer
      The 56th Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology, The 21th International Rheumatology Symposium
    • Place of Presentation
      Grand Prince Hotel New Takanawa, Tokyo
    • Related Report
      2012 Final Research Report
  • [Presentation] “Fas-FasL dependent induction of autoantibody suppressive Egr2 expressing CD4+CD25-LAG3+ regulatory T cell”2012

    • Author(s)
      Tomohisa Okamura
    • Organizer
      第56回日本リウマチ学会総会
    • Place of Presentation
      グランドプリンスホテル ニュー高輪, 東京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] "DEVELOPMENT OF AUTOANTIBODY SUPPRESSIVE EGR2 EXPRESSING CD4+CD25-LAG3+ REGULATORY T CELLS IS DEPENDENT ON FAS-FAS LIGAND INTERACTION"2012

    • Author(s)
      Tomohisa Okamura
    • Organizer
      8th International Congress on Autoimmunity
    • Place of Presentation
      Granada, Spain
    • Related Report
      2012 Annual Research Report
  • [Presentation] A critical role of CD4+CD25-LAG3+ regulatory T cells in suppression of B cells2011

    • Author(s)
      岡村僚久、藤尾圭志、渋谷美穂子、住友秀次、庄田宏文、山本一彦
    • Organizer
      第55回 日本リウマチ学会 総会・学術集会
    • Place of Presentation
      神戸ポートピアホテル・国際会議場(兵庫県)
    • Related Report
      2011 Research-status Report
  • [Presentation] A critical role of CD4+CD25-LAG3+ regulatory T cells in suppression of B cell responses2011

    • Author(s)
      岡村僚久、藤尾圭志、岡本明子、渋谷美穂子、住友秀次、庄田宏文、山本一彦
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Research-status Report
  • [Book] 「Pharma Medica」 自己免疫疾患の最近の話題と展望 特集号2013

    • Author(s)
      岡村僚久
    • Total Pages
      6
    • Publisher
      メディカルレビュー社
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 Final 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/project.html

    • Related Report
      2012 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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