High-throughput Treg cell receptor sequencing reveals the relationship between disease activity and immunosenescence in patients with rheumatoid arthritis

Treg cells play an important role in the induction of autoimmune tolerance, and their ability of antigen recognition and regulation is determined by the receptor (TCR). TCR diversity determines the autoimmune responses in RA and is closely associated with autoimmune diseases prognosis and prevention. Previous studies have found that there is immunosenescence in RA, that is, the decrease of the number of naïve CD4 ⁺ T cells and the reduction of TCR repertoire diversity. High disease activity is an independent risk factor for RA. We speculate that high disease activity is related to immunosenescence—the decline of adaptive immune function and a chronic inflammation, but its biological mechanism is still unclear and needs to be further elucidated. In this study, high-throughput Immuno-Seq sequencing and flow cytometry were used to compare normal subjects and RA patients, as well as RA patients whose disease activity changed to clinical remission after standard treatment. It was found that high disease activity not only led to a decrease in the number of naïve Treg cells, but also led to a decrease in the diversity of Treg cell receptor repertoire, weakening their ability to recognize self-antigens and induce immune tolerance, leading to the occurrence and development of RA. Besides, these characteristics of the TCR repertoire, particularly the disease activity related clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.