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Generation of novel therapeutic strategies for rheumatoid arthritis by reguIation of autoantigen-specific T cells

Research Project

Project/Area Number 24790990
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

SHODA Hirofumi  東京大学, 医学部附属病院, 助教 (20529036)

Project Period (FY) 2012 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords関節リウマチ / CD4陽性T細胞 / Bip / T細胞受容体 / 制御性T細胞 / ペプチド療 / HLA-DRエピトープ / ペプチド療法 / エピトープ
Research Abstract

We aimed to establish new therapeutic strategies against rheumatoid arthritis (RA). In order to achieve this aim, some antigen-specific T cells were analyzed in RA patients so far. We newly identified the autoantigen BiP-specific effector and regulatory T cells in RA patients. Especially, the proliferative activities of BiP-specific effector T cells significantly correlated with RA disease activities and serum titers of anti-BiP and anti-citrullinated BiP antibodies. In contrast, BiP-specific regulatory T cells suppressed the proliferation and cytokine secretion of BiP-specific effctor T cells. In addition, oral administration of the BiP-derived epitope, which were recognized by regulatory T cells in RA, could ameliorate the mouse model of arthritis by the induction of regulatory T cells. Collectively, this BiP-derived epitope could be applied for a new therapy of human diseases.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2013 2012 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (9 results) Patent(Industrial Property Rights) (2 results)

  • [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 2013 Final 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 2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 関節リウマチにおける抗原特異的T細胞応答2013

    • Author(s)
      庄田 宏文
    • Organizer
      第41回臨床免疫学会総会
    • Place of Presentation
      海峡メッセ(山口県下関市)
    • Year and Date
      2013-11-29
    • Related Report
      2013 Final Research Report
  • [Presentation] autoantigen Bip-specific regulatory T cells in rheumatoid arthritis and thier therapeutic application2013

    • Author(s)
      庄田 宏文、藤尾 圭志、山本 一彦
    • Organizer
      第57回日本リウマチ学会総会
    • Place of Presentation
      京都国際会議場(京都府京都市)
    • Year and Date
      2013-04-18
    • Related Report
      2013 Final Research Report
  • [Presentation] autoantigen Bip-specific CD4+ T cells in rheumatoid arthritis2013

    • Author(s)
      庄田 宏文、藤尾 圭志、山本 一彦
    • Organizer
      第50回日本臨床分子医学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都中央区)
    • Year and Date
      2013-04-11
    • Related Report
      2013 Final Research Report
  • [Presentation] autoantigen Bip-specific regulatory T cells in rheumatoid arthritis and thier therapeutic application2013

    • Author(s)
      庄田 宏文
    • Organizer
      第57回日本リウマチ学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Impaired homeostatic balance between autoantigen BiP-specific effector and regulatory T cells in rheumatoid arthritis2012

    • Author(s)
      庄田 宏文、藤尾 圭志、山本 一彦
    • Organizer
      第41回日本免疫学会総会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2012-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Impaired homeostatic balance between autoantigen BiP-specific effector and regulatory T cells in rheumatoid arthritis2012

    • Author(s)
      庄田 宏文
    • Organizer
      第41回日本免疫学会総会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] autoantigen Bip-specific CD4+ T cells in rheumatoid arthritis

    • Author(s)
      庄田 宏文、藤尾 圭志、山本 一彦
    • Organizer
      第50回日本臨床分子医学会学術集会.
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Annual Research Report
  • [Presentation] autoantigen Bip-specific regulatory T cells in rheumatoid arthritis and thier therapeutic application.

    • Author(s)
      庄田 宏文、藤尾 圭志、山本 一彦
    • Organizer
      第57回日本リウマチ学会総会.
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] 関節リウマチにおける抗原特異的T細胞応答

    • Author(s)
      庄田 宏文
    • Organizer
      第41回臨床免疫学会総会
    • Place of Presentation
      海峡メッセ
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] ペプチド、及びそれを含む医薬組成物2013

    • Inventor(s)
      山本 一彦、藤尾 圭志、庄田 宏文
    • Industrial Property Rights Holder
      国立大学法人 東京大学
    • Industrial Property Number
      2013-082683
    • Filing Date
      2013-04-11
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] ペプチド、及びそれを含む医薬組成物2013

    • Inventor(s)
      山本 一彦、藤尾 圭志、庄田 宏文
    • Industrial Property Rights Holder
      国立大学法人 東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-082683
    • Filing Date
      2013-04-11
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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