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FRI0016 Critical role for the IL-23/TNF-alpha axis during TLR2/NOD2 mediated acute joint inflammation
  1. F. Cornelissen,
  2. O.B.J. Corneth,
  3. P.S. Asmawidjaja,
  4. A. Mus,
  5. E. Lubberts
  1. Rheumatology, Erasmus Mc University Medical Center, Rotterdam, Netherlands

Abstract

Background IL-23 is essential in the development of chronic autoimmune diseases and supports the maturation of pathogenic Th17 cells. Although the role of IL-23 during adaptive immunity in arthritis has been studied extensively, the role of IL-23 during acute joint inflammation is unknown.

Objectives To investigate the role of IL-23 in the development of an acute, macrophage-mediated joint inflammation.

Methods Peptidoglycan (PG) or streptococcal cell wall fragments (SCW) were intra-articularly injected into the knee joint of naïve wt or IL-23p19 deficient mice. Joint swelling was assessed by measuring joint thickness using a caliper. In addition, synovial expression of different cytokines was measured by specific ELISA and/or Q-PCR. Moreover, synovial explants of wt and IL-23p19 deficient mice were stimulated with SCW and cytokine levels were measured by ELISA.

Results TLR2/NOD2-mediated streptococcal cell wall (SCW) and peptidoglycan (PG) induced acute joint inflammation in IL-23p19-deficient mice resulted in a profound reduction of local joint inflammation compared to control mice in both these models. Synovial IL-23p19 transcript was detected at 1.5 and 4 hours after arthritis induction and was further increased 1 day after PG injection with a peak at day 2. Interestingly, IL-23p19-/- mice showed a significant reduction in synovial TNF-a, but not IL-6 levels 4 hours after TLR2/NOD2-mediated arthritis induction in the knee joint. In line with this, reduced TNF-a levels were detected in the culture supernatant of SCW-stimulated synovial explants from IL-23p19-/- mice compared to control mice.

Conclusions These data show a critical role for IL-23 in the development of a TLR2/NOD2-mediated acute joint inflammation and reveal a novel IL-23/TNFalpha axis in this process.

Disclosure of Interest None Declared

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