T cells, the next big target in axSpA?

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by complex immune dysregulation, with T cells playing a central role in its pathogenesis. In this review we synthesize current knowledge on diverse T cell subsets in axSpA, their pathogenic mechanisms, and emerging therapeutic strategies targeting these cells. We highlight conventional αβ T cell receptor (TCR) expressing CD8+ T cells, CD4+ Th17and Treg cells, and CD103+CD49a+ tissue-resident memory (TRM) integrin expressing (InEx) T cells in axSpA initiation and progression. Innate-like T cell subsets, including γδ T cells, mucosal-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells alongwith innate lymphoid cells (ILC3s, though not T cells), contribute substantially via interlukin-17 (IL-17) production via IL-23, driving inflammation and tissue damage. We discuss complex milieu of cytokines in T cell-mediated inflammation, offering potential explanations for inefficacy of some cytokine inhibitors. We explore alternative drivers of inflammation and their implications for developing more effective therapies targeting T cells in axSpA, either directly via anti-TRBV9 antibody therapy or janus kinase (JAK) inhibition or indirectly by inhibiting mediators such as IL-17 and TNF. This complex interplay of T cell subsets in disease pathogenesis underscores the need for research to develop more targeted treatments, opening new avenues for personalized therapies and combination approaches that address multiple aspects of the inflammatory cascade in axSpA.