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

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790990
• 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: The 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
• 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

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.

Research Products

• [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, Fujio K, Okamura T, Yanai A, Sumitomo S, Shoda H, Tamura T, Yoshida H, Charnay P, Yamamoto K
  • Journal Title: Eur J Immunol Volume: Vol 43, No.4 Pages: 1063-1073
  • DOI: doi:10.1002/eji.201242942
  • 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: Vol 191, No.5 Pages: 2351-2359
  • DOI: doi:10.4049/jimmunol.1202106
  • 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
• [Presentation] autoantigen Bip-specific regulatory T cells in rheumatoid arthritis and thier therapeutic application (2013)
  • 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
• [Presentation] autoantigen Bip-specific CD4+ T cells in rheumatoid arthritis (2013)
  • 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
• [Presentation] Impaired homeostatic balance between autoantigen BiP-specific effector and regulatory T cells in rheumatoid arthritis (2012)
  • 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
• [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: 特許, 特願2013-82683
  • Filing Date: 2013-04-11