CCR5 mediates rheumatoid arthritis progression by promoting the activation and proliferation of non-classical Th1...

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.