The analysis of myeloid-derived suppressor cells related with the pathogenesis of rheumatoid arthritis and development of a new therapy

• Project/Area Number: 25461480
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KAWAHITO YUTAKA 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50336731)
• Co-Investigator(Kenkyū-buntansha): KOHNO MASATAKA 京都府立医科大学, 医学研究科, 講師 (60405256) ; ASHIHARA EISHI 京都薬科大学, 薬学部, 教授 (70275197) ; YAMAMOTO AIHIRO 京都府立医科大学, 医学研究科, 助教 (60589878)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 関節リウマチ / 骨髄由来抑制細胞 / MSDCs / コラーゲン誘導関節炎 / MDSCs

Outline of Final Research Achievements

In this study, MDSCs (Myeloid-derived suppressor cells) accumulated in the spleens of mice with CIA (collagen induce arthritis) when arthritis severity peaked. These MDSCs inhibited the proliferation of CD4+ T cells and their differentiation into Th17 cells in vitro. Moreover, MDSCs inhibited IFN-γ, IL-2, TNFα, and IL-6 by CD4+ T cells in vitro, which is antigen non-specific T cell response. Adoptive transfer of MDSCs reduced the severity of CIA in vivo. In conclusion, MDSCs in CIA suppress the progression of CIA by inhibiting the pro-inflammatory immune response of CD4+ T cells. These observations suggest that MDSCs play crucial roles in the regulation of autoimmune arthritis, which could be exploited in new cell-based therapies for human rheumatoid arthritis.

Research Products

• [Journal Article] Myeloid-derived suppressor cells in autoimmune diseases (2014)
  • Author(s): Fujii W, Ashihara E, Kawahito Y
  • Journal Title: Inflammation and Regeneration Volume: 34（3） Pages: 124-128
  • NAID: 130004943856
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Myeloid-Derived Suppressor Cells Play Crucial Roles in the Regulation of Mouse Collagen-Induced Arthritis. (2013)
  • Author(s): 1. Fujii W, Ashihara E, Hirai H, Nagahara H, Kajitani N, Fujioka K, Murakami K, Seno T, Yamamoto A, Ishino H, Kohno M, Maekawa T, Kawahito Y.
  • Journal Title: J Immunol Volume: 191 Issue: 3 Pages: 1073-1081
  • DOI: 10.4049/jimmunol.1203535
  • Peer Reviewed
• [Presentation] 自己免疫性疾患における骨髄由来抑制細胞の機能解析 (2014)
  • Author(s): 藤井 渉, 芦原英司, 川人 豊
  • Organizer: 第24回日本サイトメトリー学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-29
• [Presentation] 自己免疫性関節炎におけるMyeloid-derived suppressor cellsはCD4⁺T細胞の免疫反応を抑制し、関節炎を改善させる. (2013)
  • Author(s): 藤井 渉、永原秀剛、藤岡数記、村上 憲、中村 薫、妹尾高宏、山本相浩、石野秀岳、河野正孝、小田 良、徳永大作、久保俊一、川人 豊.
  • Organizer: 第57回日本リウマチ学会総会・学術総会
  • Place of Presentation: 京都
• [Presentation] Myeloid-derived suppressor cells have reguratory roles in mouse collagen-induced arthritis. (2013)
  • Author(s): Fujii W, Ashihara E, Hirai H, Nagahara H, Fujioka K, Murakami K, Nakamura K, Seno T, Yamamoto A, Ishino H, Kohno M,Maekawa T, Kawahito Y.
  • Organizer: The annual European Congress of Rheumatology 2013
  • Place of Presentation: Madrid, Spain
• [Presentation] Myeloid-derived suppressor cells play crucial roles in the regulation of mouse collagen-induced arthritis. (2013)
  • Author(s): Fujii W, Ashihara E, Hirai K, Fujioka K, Seno T, Ishino H, Kawahito Y.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉