Analysis of CD8+ regulatory T cells in elderly-onset rheumatoid arthritis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17418
• 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: Osaka Metropolitan University (2022); Osaka City University (2021); Kyoto University (2020)
• Principal Investigator: Ryu Watanabe 大阪公立大学, 大学院医学研究科, 講師 (40723218)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Rheumatoid arthritis / Regulatory T cells / Synovitis

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.

Free Research Field

Rheumatology

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。