The initiation, but not the persistence, of experimental spondyloarthritis is dependent on interleukin-23 signaling

Melissa N. van Tok, Songqing Na, Christopher R. Lao, Marina Alvi, Desirée Pots, Marleen G.H. van de Sande, Joel D. Taurog, Jonathon D. Sedgwick, Dominique L. Baeten, Leonie M. van Duivenvoorde

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56 Scopus citations


IL-17A is a central driver of spondyloarthritis (SpA), its production was originally proposed to be IL-23 dependent. Emerging preclinical and clinical evidence suggests, however, that IL-17A and IL-23 have a partially overlapping but distinct biology. We aimed to assess the extent to which IL-17A-driven pathology is IL-23 dependent in experimental SpA. Experimental SpA was induced in HLA-B27/Huβ2m transgenic rats, followed by prophylactic or therapeutic treatment with an anti-IL23R antibody or vehicle control. Spondylitis and arthritis were scored clinically and hind limb swelling was measured. Draining lymph node cytokine expression levels were analyzed directly ex vivo, and IL-17A protein was measured upon restimulation with PMA/ionomycin. Prophylactic treatment with anti-IL23R completely protected against the development of both spondylitis and arthritis, while vehicle-treated controls did develop spondylitis and arthritis. In a therapeutic study, anti-IL23R treatment failed to reduce the incidence or decrease the severity of experimental SpA. Mechanistically, expression of downstream effector cytokines, including IL-17A and IL-22, was significantly suppressed in anti-IL23R versus vehicle-treated rats in the prophylactic experiments. Accordingly, the production of IL-17A upon restimulation was reduced. In contrast, there was no difference in IL-17A and IL-22 expression after therapeutic anti-IL23R treatment. Targeting the IL-23 axis during the initiation phase of experimental SpA-but not in established disease-inhibits IL-17A expression and suppresses disease, suggesting the existence of IL-23-independent IL-17A production. Whether IL-17A can be produced independent of IL-23 in human SpA remains to be established.

Original languageEnglish (US)
Article number1550
JournalFrontiers in immunology
Issue numberJUL
StatePublished - Jul 9 2018


  • Animal models
  • Experimental spondyloarthritis
  • HLA-B27 tg rats
  • IL-17A
  • IL-23 signaling
  • IL-23R
  • Spondyloarthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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