T cells, the Next Big Target in Axial Spondyloarthritis?

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-expressing CD8+ T cells, CD4+ Th17 cells and Treg cells, and CD103+CD49a+ tissue-resident memory integrin-expressing T cells in axSpA initiation and progression. Innate-like T cell subsets, including γδ T cells, mucosal-associated invariant T cells, and invariant natural killer T cells, along with innate lymphoid cells (though not T cells), contribute substantially via interlukin-17 (IL-17) production via IL-23, driving inflammation and tissue damage. We discuss a 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 JAK inhibition or indirectly by inhibiting mediators such as IL-17 and tumor necrosis factor. 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.