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Analysis of Egr2-expressing regulatory T cells in mice and human

Research Project

Project/Area Number 24390252
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionThe University of Tokyo

Principal Investigator

FUJIO KEISHI  東京大学, 医学部附属病院, 講師 (70401114)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords自己免疫疾患 / 制御性T細胞 / TGF-beta / 免疫抑制療法 / サイトカイン / 自己反応性B細胞 / JAKキナーゼ / STAT / 抗体産生
Outline of Final Research Achievements

We previously described that CD4+CD25-LAG3+regulatory T cells(LAG3+ Treg) are regulated by Egr2, a zinc-finger transcription factor required for the
induction of T-cell anergy.We herein demonstrate that LAG3+Treg produce high amounts ofTGF-beta3 in an Egr2- and Fas-dependent manner. LAG3+Treg require TGF-beta3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-beta3- and LAG3+Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-beta3-expressing human LAG3+Treg suppress antibody production and that SLE patients exhibit decreased frequencies of LAG3+Treg. These results clarify the mechanism of B-cell regulation and suggest therapeutic strategies.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (21 results)

All 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 2 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses2015

    • Author(s)
      Okamura T, Sumitomo S, Morita K, Iwasaki Y, Inoue M, Nakachi S, Komai T, Shoda H, Miyazaki J, Fujio K, Yamamoto K.
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 1-14

    • DOI

      10.1038/ncomms7329

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulatory T cells in systemic lupus erythematosus2015

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

      Japanese Journal of Clinical Immunology

      Volume: 38 Issue: 1 Pages: 69-77

    • DOI

      10.2177/jsci.38.69

    • NAID

      130004875954

    • ISSN
      0911-4300, 1349-7413
    • Related Report
      2014 Annual Research Report
    • Open Access
  • [Journal Article] Interleukin-27 in T cell immunity.2015

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

      Int J Mol Sci

      Volume: 16 Issue: 2 Pages: 2851-63

    • DOI

      10.3390/ijms16022851

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Egr2 and Egr3 are the unique regulators for systemic autoimmunity.2013

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

      JAKSTAT.

      Volume: 2 Issue: 4 Pages: 1060-1060

    • DOI

      10.1002/art.38330

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcription factor early growth response 3 is associated with the TGF-β1 expression and the regulatory activity of CD4-positive T cells in vivo.2013

    • Author(s)
      Sumitomo S, Fujio K, Okamura T, Morita K, Ishigaki K, Suzukawa K, Kanaya K, Kondo K, Yamasoba T, Furukawa A, Kitahara N, Shoda H, Shibuya M, Okamoto A, Yamamoto K.
    • Journal Title

      J Immunol

      Volume: 191 Issue: 5 Pages: 2351-9

    • DOI

      10.4049/jimmunol.1202106

    • Related Report
      2013 Annual 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
      2013 Annual Research Report 2012 Annual 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
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kidney-infiltrating T cell clones promote nephritis in lupus-prone mice2012

    • Author(s)
      Okamoto A, Fujio K, Tsuno NH, Takahashi K, Yamamoto K
    • Journal Title

      Kidney Int.

      Volume: 8 Issue: 9 Pages: 969-79

    • DOI

      10.1038/ki.2012.242

    • Related Report
      2012 Annual 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
    • Peer Reviewed
  • [Presentation] TGF-beta3-expressing CD4+CD25-LAG3+ regulatory T cells control humoral immune responses.2014

    • Author(s)
      Keishi Fujio.
    • Organizer
      第43回日本免疫学会学術総会 国際シンポジウム
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] TGF-beta3産生によるCD4陽性CD25陰性LAG3陽性制御性T細胞のB細胞機能抑制2014

    • Author(s)
      藤尾圭志
    • Organizer
      第79回日本インターフェロンサイトカイン学会
    • Place of Presentation
      北海道大学
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CD4+CD25-LAG3+ regulatory T cells and systemic autoimmunity.2014

    • Author(s)
      Keishi Fujio, Tomohisa Okamura, Kaoru Morita, Mariko Inoue, Yukiko Iwasaki, Shuji Sumitomo, Shinichiro Nakachi, Kazuhiko, Yamamoto.
    • Organizer
      第58回日本リウマチ学会(東京)国際リウマチシンポジウム
    • Place of Presentation
      新高輪プリンスホテル
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 全身性エリテマトーデスと免疫制御細胞2013

    • Author(s)
      藤尾圭志
    • Organizer
      第57回日本リウマチ学会総会 シンポジウム
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] The B cell control by EGR-2 expressing CD4+CD25-LAG3+ regulatory T cells2013

    • Author(s)
      Keishi Fujio
    • Organizer
      Autoimmunity Congress Asia
    • Place of Presentation
      Hong Kong Academy of Science
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] The role of CD4+CD25-LAG3+ regulatory T cells in autoimmune diseses2013

    • Author(s)
      Keishi Fujio
    • Organizer
      Annual Meeting of Japanease Society for Immunology, 2013
    • Place of Presentation
      Makuhari Messe
    • Related Report
      2013 Annual Research Report
  • [Presentation] CD4+CD25-LAG3+ regulatory T cells and autoimmunity2012

    • Author(s)
      KEISHI FUJIO (invited)
    • Organizer
      8^<th> International Congress on Autoimmunity Satellite Symposium: Recent Progress in Autoimmune Research in Japan
    • Place of Presentation
      Granada, Spain
    • Year and Date
      2012-05-10
    • Related Report
      2012 Annual Research Report
  • [Presentation] 制御性T細胞と自己免疫2012

    • Author(s)
      藤尾圭志
    • Organizer
      第56回日本リウマチ学会総会
    • Place of Presentation
      高輪、東京
    • Year and Date
      2012-04-27
    • Related Report
      2012 Annual Research Report
  • [Remarks] 東京大学医学部アレルギー・リウマチ内科 第18研究室

    • URL

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

    • Related Report
      2014 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
      2013 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] B細胞活性化の抑制剤及び自己免疫疾患の治療剤2014

    • Inventor(s)
      藤尾圭志、岡村僚久、山本一彦、森田薫、駒井俊彦
    • Industrial Property Rights Holder
      藤尾圭志、岡村僚久、山本一彦、森田薫、駒井俊彦
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-11-28
    • Related Report
      2014 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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