GLI3 in rheumatoid arthritis synovial fibroblasts

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20755
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Komiya Yoji 東京医科歯科大学, 東京医科歯科大学病院, 特任助教 (00907818)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 関節リウマチ / 滑膜線維芽細胞

Outline of Final Research Achievements

DMARDs are used for the treatment of rheumatoid arthritis(RA). Some patients do not respond to any of these drugs, and infections associated with immunosuppression are also a problem. In RA, synovial fibroblasts (RASF) maintain chronic inflammation which leads to joint destruction. There are no therapeutic agents that target RASF. CD34-THY1+ subset is expanded in RASF and has characteristic features of invasive cells and dominant producer of inflammatory cytokines, suggesting that this subset is pathogenic. GLI3 was highly expressed in the CD34-THY1+. Silencing of GLI3 by siRNA in RASF decreased the proliferation, migration, and production of inflammatory mediators. GLI3 would be a key transcription factor to regulate the pathogenic functions of the CD34-THY1+ fibroblast subset in RA.

Free Research Field

膠原病・リウマチ内科学分野

Academic Significance and Societal Importance of the Research Achievements

関節リウマチに対する新規治療標的として、関節リウマチ由来滑膜線維芽細胞の中で細胞浸潤、増殖能の高いサブセットの抑制は、RASFを標的とした新規治療戦略の開発に繋がると考えた。siRNAを用いた結果GLI3は滑膜線維芽細胞からの種々のサイトカイン産生と増殖、遊走能を担った。GLI3は滑膜線維芽細胞からの種々のサイトカイン産生と増殖、遊走能を担う転写因子と考えられる。