title: Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ T cells in patients with active ankylosing spondylitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Kenna
authors.forename: Stuart I
authors.initials: SI
authors.lastname: Davidson
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.forename: Linda A
authors.initials: LA
authors.lastname: Bradbury
authors.forename: Janelle
authors.initials: J
authors.lastname: McFarlane
authors.forename: Malcolm
authors.initials: M
authors.lastname: Smith
authors.forename: Helen
authors.initials: H
authors.lastname: Weedon
authors.forename: Shayna
authors.initials: S
authors.lastname: Street
authors.forename: Ranjeny
authors.initials: R
authors.lastname: Thomas
authors.forename: Gethin P
authors.initials: GP
authors.lastname: Thomas
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D015398:Signal Transduction; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; C515500:IL23R protein, human; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin