Construction of an analysis system for antigen-specific immune response in human autoimmunity

• Project/Area Number: 25670459
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: The University of Tokyo
• Principal Investigator: FUJIO KEISHI 東京大学, 医学部附属病院, 講師 (70401114)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自己抗原 / T細胞レセプター / 次世代シークエンス / 関節リウマチ / 遺伝子発現解析

Outline of Final Research Achievements

The aim of this project is to analyze the kinetics of autoreactive T cells in autoimmunity using T cell receptor. We performed single-cell transcriptome analysis and TCR repertoire analysis using next-generation sequence in peripheral blood and synovium CD4+ T cells in rheumatoid arthritis (RA). Expanded clones in the joint belonged to CXCR3-CCR6-CXCR5- fraction in the peripheral blood, and they aquired CXCR4 expression and senescent phenotype in the synovium. In the multicolor flowcytometory-based clinical database revealed that CXCR4+ memory T cells are closely associated with disease activity in RA. This research clarified the previously unknown kinetics of pathgenic CD4+ T cell clone in RA.

Research Products

• [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: 2 Pages: e23952-e23952
  • DOI: 10.4161/jkst.23952
  • 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
  • Peer Reviewed
• [Journal Article] Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells (2013)
  • Author(s): Iwasaki, Y.
  • Journal Title: Eur J Immunol Volume: undefined Issue: 4 Pages: 1063-73
  • DOI: 10.1002/eji.201242942
  • 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 Issue: suppl 2 Pages: 1-8
  • DOI: 10.1136/annrheumdis-2012-202341
  • Peer Reviewed
• [Presentation] 関節リウマチの病態に関与するCD4陽性T細胞クローンの同定 (2014)
  • Author(s): 石垣和慶、庄田宏文、高地雄太、安井哲郎、門野夕峰、田中栄、藤尾圭志ほか
  • Organizer: 第42回日本臨床免疫学会総会
  • Place of Presentation: 京王プラザホテル 東京
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 関節リウマチ患者における包括的臨床免疫解析の試み (2014)
  • Author(s): 永渕泰雄、庄田宏文、住友秀次、仲地真一郎、加藤里佳、土田優美、ほか
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: 新高輪プリンスホテル 東京
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 関節リウマチの病態に関与するCD4陽性T細胞クローンの候補の同定 (2014)
  • Author(s): 石垣和慶、庄田宏文、高地雄太、藤尾圭志、安井哲郎、門野夕峰ほか
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: 新高輪プリンスホテル 東京
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Unbiased TCR repertoire anlaysis in rheumatoid arthritis patients by combination of single-cell and next generation sequencing (2013)
  • Author(s): Ishigaki Kazuyoshi, Shoda Hirofumi, Kochi Yuta, Fujio Keishi, Yamamoto K
  • Organizer: Annual Meeting of the Japanese Society for Immunology 2013
  • Place of Presentation: MAKUHARI MESSE
• [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/