Department of Clinical Immunology, Xijing Hospital, and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Int J Rheum Dis. 2024 Nov;27(11):e15370. doi: 10.1111/1756-185X.15370.
Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by immune dysegulation, including an immune imbalance due to abnormal activation of non-classical Th1 cells (CD161 Th1). This study investigated the effects of CCR5 on the activation and proliferation of CD161 Th1 and their pathogenicity in patients with RA.
The study was conducted on 53 patients with RA and 32 age- and sex-matched healthy controls (HC). The cell phenotype was assessed by flow cytometry and the cytokine levels in the supernatant were detected by ELISA.
We demonstrate a marked increase in CD161 Th1 cells in the synovial fluid of RA patients. These cells exhibit a hyperactivated and hyperproliferative state alongside elevated CCR5 expression. Furthermore, the levels of CD161 Th1 cells, CD25, and CCR5 in RA synovial fluid show a positive correlation with the disease activity. Additionally, our study reveals that CCR5 facilitates the activation, proliferation, and cytokine production of CD161 Th1 cells through the pZAP70/NFAT signaling pathway.
These findings contribute to a deeper understanding of RA pathogenesis and uncover a novel mechanism that regulates non-classical CD161 Th1 responses in RA, which may provide a potential therapeutic target.
类风湿关节炎（RA）是一种常见的自身免疫性疾病，其特征为免疫失调，包括由于非经典 Th1 细胞（CD161 Th1）异常激活导致的免疫失衡。本研究旨在探讨 CCR5 对 CD161 Th1 的激活和增殖及其在 RA 患者发病机制中的作用。
该研究纳入了 53 例 RA 患者和 32 名年龄和性别匹配的健康对照者（HC）。采用流式细胞术评估细胞表型，ELISA 检测上清液中细胞因子水平。
我们发现 RA 患者关节滑液中 CD161 Th1 细胞明显增加。这些细胞表现出过度激活和增殖状态，同时伴有 CCR5 表达升高。此外，RA 关节滑液中 CD161 Th1 细胞、CD25 和 CCR5 的水平与疾病活动度呈正相关。此外，我们的研究表明 CCR5 通过 pZAP70/NFAT 信号通路促进 CD161 Th1 细胞的激活、增殖和细胞因子产生。
这些发现有助于深入了解 RA 的发病机制，并揭示了一种调节 RA 中非经典 CD161 Th1 反应的新机制，可能为治疗提供新的靶点。
