Regulatory T cells in axial spondyloarthritis

Type 3 immunity underlies both pain and inflammation in axial spondyloarthritis (axSpA), with IL-17A-producing cells such as T-helper 17 cells (TH17) being pathogenic mediators. In contrast, the role regulatory T cells (Tregs) have in maintaining immune homeostasis in axSpA remains poorly defined. Although understudied, emerging research suggests three plausible hypotheses: 1) Tregs in axSpA could be functional but are turned off in response to external signals. 2) Tregs in axSpA have deficiencies that result in reduced suppressive capabilities or stability. 3) Tregs directly contribute to autoimmunity through cytotoxicity. These hypotheses are further examined across gut, skin and joint to contextualize extra-articular manifestations and disease heterogeneity. This framework highlights critical gaps in current knowledge and identifies actionable pathways for translating Treg biology into novel therapeutic strategies. This review summarizes the role of FOXP3 in Treg plasticity, stability and function in axial spondyloarthritis, proposing that Treg dysregulation may contribute to disease pathogenesis and clinical manifestations.