Identification of autoantigens recognized by pathogenic T cells in autoimmune arthritis

• Project/Area Number: 24790996
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kyoto 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: ¥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.

Research Products

• [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
  • 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
  • Peer Reviewed
• [Presentation] An arthritogenic TCR obtained from CD4+ T cells in spontaneous autoimmune arthritis (2014)
  • 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
• [Presentation] Cloning of an arthritogenic TCR from CD4+ T cells in spontaneous autoimmune arthritis (2014)
  • Author(s): Yoshinaga Ito
  • Organizer: Keystone symposia, Inflammatory Disease: Recent Advances in Basic and Translational Research and Therapeutic Treatments
  • Place of Presentation: Vancouver, Canada
• [Presentation] An arthritogenic TCR obtained from CD4+ T cells in spontaneous autoimmune arthritis (2013)
  • Author(s): Yoshinaga Ito
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ、千葉
• [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