The roles of FGFR1-expressing helper T cells in the pathogenesis of rheumatoid arthritis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16297
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Chiba University
• Principal Investigator: Tanaka Shigeru 千葉大学, 医学部附属病院, 助教 (30822051)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 関節リウマチ / FGFR1

Outline of Final Research Achievements

It is well known that CD4+ T cells have roles in the pathogenesis of rheumatoid arthritis. However, the precise mechanisms are not well understood. We previously discovered that FGFR1 is a characteristic feature of CD4+ T cells from treatment-naive rheumatoid arthritis patient, and interestingly, the signal is diminished after the treatment.This study aimed to explore the characteristics of FGFR1-expressing CD4+ T cells in the patients with rheumatoid arthritis.
We performed single cell RNA-seq analysis and found FGFR1-expressing cells have activated phenotype. Consistent with this, flow cytometric analyses revealed that FGFR1-expressing CD4+ T cells have terminally differentiated phenotype with high production of inflammatory cytokines.
These results suggest that FGFR1-expressing CD4+ T cells have a potential to deteriorate the joint inflammation. Also, FGFR1+ CD4+ T cells may be a candidate for the novel therapeutic target.

Free Research Field

リウマチ学

Academic Significance and Societal Importance of the Research Achievements

関節リウマチは多数の関節に炎症が生じて、痛みや動きに支障が生じる疾患である。近年、薬物治療の進歩によって症状が改善する患者が増えているが、依然として症状の残る人もおり、新たな治療戦略が求められている。本研究ではFGFR1を発現するヘルパーT細胞に着目し、その機能を解析した。FGFR1陽性ヘルパーT細胞は活性化している形質を持っており、特に炎症物質を多く産生する機能があることが明らかとなった。今後、FGFR1陽性ヘルパーT細胞を標的とした治療法が確立されることで、既存の治療で改善しない関節リウマチ患者に新たな治療法を提案できる可能性がある。