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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