Analysis of CD8+ regulatory T cells in elderly-onset rheumatoid arthritis
| Project/Area Number |
20K17418
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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 | Osaka Metropolitan University (2022)
Osaka City University (2021)
Kyoto University (2020) |
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Principal Investigator |
Ryu Watanabe 大阪公立大学, 大学院医学研究科, 講師 (40723218)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Rheumatoid arthritis / Regulatory T cells / Synovitis / 高齢発症関節リウマチ / CD8+制御性T細胞 / CD4+制御性T細胞 / 滑膜炎 / 制御性T細胞 |
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| Outline of Research at the Start |
関節リウマチ（RA）は、40～50代の女性に好発するが、近年、60歳を超えて発症する症例（高齢発症RA）が増えており、60歳以下で発症する若年発症RAと比べ、疾患活動性が高く、関節破壊の進行が早いことが報告されている。しかし、その機序は明らかではない。
制御性T細胞は過剰な免疫応答の抑制に働くT細胞サブセットで、CD4陽性（CD4 Treg）とCD8陽性（CD8 Treg）の二群に分けられるが、老化に伴って、特にCD8 Tregの機能が低下する。高齢発症RAは若年発症RAに比べ、CD8 Tregの機能不全のため疾患活動性が高く、関節破壊が進みやすいという仮説を検証する。
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| Outline of Final Research Achievements |
A total of 40 patients (EORA, n = 17; YORA, n = 23) were cross-sectionally enrolled. Current disease activity and treatment were comparable between the two groups; however, levels of multiple cytokines, including IL-1, TNF, interferon (IFN)-g, IL-2, and IL-10, were significantly increased in EORA. The number of CD4+ Tregs did not differ between the groups, but those of CD8+ Tregs were significantly decreased in EORA (p = 0.0033). The number of CD8+ Tregs were inversely correlated with plasma matrix metalloprotease (MMP)-3 levels (r = -0.3331, p = 0.036). Our study results revealed an intrinsic deficiency of CD8+ Tregs in patients with EORA, which leaves synovitis unchecked with excessive MMP-3 release.
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| Academic Significance and Societal Importance of the Research Achievements |
我々の研究は、EORA患者のCD8+ Tregの欠乏を世界で初めて明らかにし、そのため、滑膜炎が抑制されず、MMP-3が過剰に放出されている可能性を報告した。そのため、今後、CD8+ Tregを回復させる治療法が、EORAの新たな治療戦略となりうる可能性がある。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] CD8+ Regulatory T Cell Deficiency in Elderly-Onset Rheumatoid Arthritis.2023
Author(s)
Watanabe R, Kadoba K, Tamamoto A, Murata K, Murakami K, Onizawa H, Fujii T, Onishi A, Tanaka M, Ito H, Morinobu A, Hashimoto M.
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Journal Title
Journal of Clinical Medicine
Volume: 12(6)
Issue: 6
Pages: 2342-2342
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prevalence of anxiety and depression in patients with rheumatoid arthritis before and during the COVID-19 pandemic2021
Author(s)
Itaya T, Torii M, Hashimoto M, Tanigawa K, Urai Y, Kinoshita A, Nin K, Jindai K, watanabe R, Murata K, Murakami K, Tanaka M, Ito H, Matsuda S, Morinobu A
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Journal Title
Reumatology
Volume: 60（4）
Issue: 4
Pages: 2023-2024
DOI
Related Report
Peer Reviewed
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[Presentation] CD8+ regulatory T cell deficiency in elderly-onset rheumatoid arthritis: A cross-sectional study in the KURAMA cohort2022
Author(s)
Watanabe R, Kadoba K, Tamamoto A, Murata K, Murakami K, Onizawa H, Fujii T, Onishi A, Tanaka M, Ito H, Morinobu A, Hashimoto M.
Organizer
24th Asia-Pacific League of Associations for Rheumatology Congress 2022
Related Report
Int'l Joint Research
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