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Identification of autoantigens recognized by pathogenic T cells in autoimmune arthritis

Research Project

Project/Area Number 24790996
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 InstitutionKyoto University

Principal Investigator

ITO Yoshinaga  京都大学, 再生医科学研究所, 助教 (60614013)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords自己抗原 / 自己反応性T細胞 / 自己免疫性関節炎 / 疾患惹起性T細胞
Outline of Final Research Achievements

T cells mediating autoimmune diseases, such as rheumatoid arthritis (RA), are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self-antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate T cells mediating autoimmune arthritis, we have isolated arthritogenic TCRs and characterized the self-antigens they recognized. One of them was the ubiquitously expressed 60S ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our understanding of the underlying drivers of autoimmunity.

Report

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

    (6 results)

All 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease.2014

    • Author(s)
      Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali DA, Kappler JW, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S.
    • Journal Title

      Science

      Volume: 364 Pages: 363-368

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TREG-cell therapies for autoimmune rheumatic diseases.2014

    • Author(s)
      Miyara M, Ito Y, Sakaguchi S
    • Journal Title

      Nat Rev Rheumatol

      Volume: 10 Pages: 543-551

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] An arthritogenic TCR obtained from CD4+ T cells in spontaneous autoimmune arthritis2014

    • Author(s)
      Yoshinaga Ito
    • Organizer
      The 9th International Symposium of the Institute Network
    • Place of Presentation
      大阪大学
    • Year and Date
      2014-06-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cloning of an arthritogenic TCR from CD4+ T cells in spontaneous autoimmune arthritis2014

    • Author(s)
      Yoshinaga Ito
    • Organizer
      Keystone symposia, Inflammatory Disease: Recent Advances in Basic and Translational Research and Therapeutic Treatments
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] An arthritogenic TCR obtained from CD4+ T cells in spontaneous autoimmune arthritis2013

    • Author(s)
      Yoshinaga Ito
    • Organizer
      日本免疫学会
    • Place of Presentation
      幕張メッセ、千葉
    • Related Report
      2013 Research-status Report
  • [Remarks] T細胞が体内のどのタンパク質を標的として関節リウマチを起こすかを特定

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2014/141017_1.html

    • Related Report
      2014 Annual Research Report

URL: 

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

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