Mechanisms and exhaustion of T follicular regulatory cells in rheumatoid arthritis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02959
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: University of Tsukuba
• Principal Investigator: Matsumoto Isao 筑波大学, 医学医療系, 教授 (30343081)
• Co-Investigator(Kenkyū-buntansha): 渋谷 和子 筑波大学, 医学医療系, 教授 (00302406)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 関節リウマチ / 高齢化 / 制御性T細胞

Outline of Final Research Achievements

T cells are considered to be important in rheumatoid arthritis (RA). In recent years, it has been said that RA is caused by aging, and an increase in IL-6 has been pointed out. However, a decrease in the function of regulatory T cells (Treg) has been reported in RA, and the eQTL effect of Treg is high. In our previous research, we found a correlation between the age of onset of RA and the number of Tregs, and in the GIA model, the pathology worsened in older mice, accompanied by an increase in Tregs and IL-6, and even when Tregs were depleted, there was little arthritis change, so a decrease in Treg function was assumed. We performed RNAseq on human Tregs and scRNAseq on CD4+ T cells in GIA lymph nodes, and found an increase in DEGs in older Tregs, an enhancement of the type I IFN pathway in pathway analysis, and changes in costimulatory molecules.

Free Research Field

膠原病リウマチアレルギー内科学

Academic Significance and Societal Importance of the Research Achievements

高齢発症病態・高齢化などから、RAにおいても生命にかかわる重篤な感染症や悪性腫瘍の発現が報告されている。また、休薬は可能なものの、薬剤を中止することが困難な疾患である。未だ病因が不明のRAであるが、より病因の根底を理解し、ターゲットを絞った副作用の少ない薬剤の開発が望まれており、高齢化社会においての臨床への貢献度は極めて高いと考える。