The roles of FGFR1-expressing helper T cells in the pathogenesis of rheumatoid arthritis.
| Project/Area Number |
21K16297
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Chiba University |
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Principal Investigator |
Tanaka Shigeru 千葉大学, 医学部附属病院, 助教 (30822051)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 関節リウマチ / FGFR1 / ヘルパーT細胞 |
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| Outline of Research at the Start |
関節リウマチは多数の関節に炎症を来し、関節機能の低下が問題となる病気である。近年、薬物治療の進歩により症状の改善する患者が増えてきているが、効果が不十分の患者が相当数存在することから、新たな治療法が必要である。本研究ではFGFR1と呼ばれる分子に注目し、炎症性関節炎の発症に関与する免疫機能をFGFR1が調節していると仮説を立てた。そこで実験的な関節炎および関節リウマチ患者の滑膜組織等を用いてその仮説を検証する。本研究により、既存の治療薬とは全く異なる新規の治療ターゲット候補を見出し、次世代の関節リウマチ治療戦略の基盤を構築する。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Epithelial cell-derived cytokine TSLP modulates metabolic program of regulatory T cells by enhancing fatty acid uptake to suppress the intestinal inflammation2023
Author(s)
Kasuya T., Tanaka S., Etori K., Shoda J., Hattori K., Endo Y., Kitajima M., Kageyama T., Iwamoto T., Yokota M., Iwata A., Suto A., Suzuki K., Suzuki H., Ziegler SF., and Nakajima H
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Journal Title
Sci. Rep.
Volume: 13
Issue: 1
Pages: 1653-1653
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Immunological features that associate with the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-22022
Author(s)
Kageyama Takahiro, Tanaka Shigeru, Etori Keishi, Hattori Koto, Miyachi Kazusa, Kasuya Tadamichi, Iwamoto Taro, Ikeda Kei, Igari Hidetoshi, Yokote Koutaro, Nakajima Hiroshi
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Journal Title
Vaccine
Volume: -
Issue: 14
Pages: 2129-2133
DOI
Related Report
Peer Reviewed
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[Journal Article] Suppressor of cytokine signalling 3 (SOCS3) expressed in podocytes attenuates glomerulonephritis and suppresses autoantibody production in an imiquimod-induced lupus model2021
Author(s)
Fukuta M, Suzuki K, Kojima S, Yabe Y, Suzuki K, Iida K, Yamada H, Makino S, Iwata A, Tanaka S, Iwamoto T, Suto A, Nakagomi D, Wakashin H, Maezawa Y, Maezawa Y, Takemoto M, Asanuma K, Nakajima H.
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Journal Title
Lupus Sci Med.
Volume: 8
Issue: 1
Pages: 426-426
DOI
Related Report
Peer Reviewed / Open Access
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