Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive [gamma]/[delta] T cells in patients with active ankylosing spondylitis

Tony Kenna, Stuart Davidson, Ran Duan, Linda Bradbury, Janelle McFarlane, Malcolm Smith, Helen Weedon, Shayna Street, Ranjeny Thomas, Gethin Thomas, Matthew Brown

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    Abstract

    Objective 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. Methods 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. Results 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. Conclusion 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.

    Original languageEnglish
    Pages (from-to)1420-1429
    Number of pages10
    JournalArthritis and Rheumatism
    Volume64
    Issue number5
    DOIs
    Publication statusPublished - 2012

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    Kenna, T., Davidson, S., Duan, R., Bradbury, L., McFarlane, J., Smith, M., Weedon, H., Street, S., Thomas, R., Thomas, G., & Brown, M. (2012). Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive [gamma]/[delta] T cells in patients with active ankylosing spondylitis. Arthritis and Rheumatism, 64(5), 1420-1429. https://doi.org/10.1002/art.33507