Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ T cells in patients with active ankylosing spondylitis

Arthritis Rheum. 2012 May;64(5):1420-9. doi: 10.1002/art.33507.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Psoriatic / diagnosis
  • Arthritis, Psoriatic / immunology
  • Arthritis, Psoriatic / metabolism
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Humans
  • Interleukin-17 / metabolism*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Receptors, Interleukin / metabolism*
  • Signal Transduction
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / metabolism*
  • Young Adult


  • Cytokines
  • IL23R protein, human
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin