Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin‐23 (IL‐23) signaling in AS pathogenesis.

The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL‐23 receptor (IL‐23R) expression in T cells was determined in each subject group, and expression levels were compared.

The proportion of IL‐23R–expressing T cells in the periphery was 2‐fold higher in AS patients than in healthy controls, specifically driven by a 3‐fold increase in IL‐23R–positive γ/δ T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL‐17 were unchanged. This increased IL‐23R expression on γ/δ T cells was also associated with enhanced IL‐17 secretion, with no observable IL‐17 production from IL‐23R–negative γ/δ T cells in AS patients. Furthermore, γ/δ T cells from AS patients were heavily skewed toward IL‐17 production in response to stimulation with IL‐23 and/or anti‐CD3/CD28.

Recently, mouse models have shown IL‐17–secreting γ/δ T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL‐23 is a maturation and growth factor for IL‐17–producing cells, increased IL‐23R expression may regulate the function of this putative pathogenic γ/δ T cell population.