FRI0016 Critical role for the IL-23/TNF-alpha axis during TLR2/NOD2 mediated acute joint inflammation. (23rd January 2014)

• Record Type: Journal Article
• Authors: Cornelissen, F.; Corneth, O.B.J.; Asmawidjaja, P.S.; Mus, A.; Lubberts, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 315
• Page End: 315
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.2473
• Languages: English
• ISSNs: 0003-4967

Abstract

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