Exploratory research on novel therapeutic targets using synovial fibroblasts derived from patients with rheumatoid arthritis

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16275
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tsuchiya Haruka 東京大学, 医学部附属病院, 特任講師 (50868560)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 関節リウマチ / 滑膜線維芽細胞 / MTF-1

Outline of Final Research Achievements

We performed in vitro analysis using primary synovial fibroblasts (SFs) derived from patients with rheumatoid arthritis (RA), and revealed that the MTF-1 inhibitor suppresses the expression of inflammatory mediators (i.e., IL-6, CCL5) from activated SFs. In addition, an in vivo analysis using the collagen-induced arthritis (CIA) model demonstrated that the MTF-1 inhibitor had the effect of suppressing the progression of arthritis. These results suggest that inhibition of MTF-1 activity could regulate arthritis by modifying the production of inflammatory mediators derived from SFs.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、MTF-1のSFsにおけるin vitroおよびin vivoの機能解析を通じて、この転写因子の活性阻害がSFsからの炎症性メディエーターの発現を修飾し、動物モデルにおける関節炎を制御することを明らかにした。本研究により、炎症や骨軟骨破壊を引き起こすSFsを標的とした創薬候補が発見されたことで、既存の薬剤とは全く異なる経路を介した、より全身的な免疫抑制作用の少ない治療開発につながることが期待される。