Unraveling immune cell heterogeneity in autoimmune arthritis: insights from single-cell RNA sequencing

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of immune-mediated arthritis, which comprises rheumatoid arthritis and spondyloarthritis. This review outlines the key findings and advancements in scRNA-seq studies focused on the pathogenesis of autoimmune arthritis and its clinical application. In rheumatoid arthritis, scRNA-seq has elucidated the heterogeneity among synovial fibroblasts and immune cell subsets in inflammatory sites, offering insights into disease mechanisms and the differences in treatment responses. Various studies have identified distinct synovial fibroblast subpopulations, such as THY1⁺ inflammatory and THY1^- destructive fibroblasts. Furthermore, scRNA-seq has revealed diverse T cell profiles in the synovium, including peripheral helper T cells and clonally expanded CD8⁺ T cells, shedding light on potential therapeutic targets and predictive markers of treatment response. Similarly, in spondyloarthritis, particularly psoriatic arthritis and ankylosing spondylitis, scRNA-seq studies have identified distinct cellular profiles associated with disease pathology. Challenges such as cost and sample size limitations persist, but collaborative efforts and utilization of public databases hold promise for overcoming these obstacles. Overall, scRNA-seq emerges as a powerful tool for dissecting cellular heterogeneity and driving precision medicine in immune-mediated arthritis.