OP0272 Inflammation at barrier tissues such as skin and gut triggers mild joint inflammation and is influenced by biomechanical stress induced by forced-running

Background The factors triggering the onset of psoriatic arthritis (PsA) and other forms of spondyloarthritis (SpA) are mostly unknown. These joint diseases are clinically associated with psoriasis (PsO) and inflammatory bowel disease (IBD). The three pathologies share the common leitmotiv of chronic inflammation and all of them have an at least partially shared genetic susceptibility. Entheses, the attachment sites of tendons and ligaments into the bones, are considered as a primary disease localization and a site of biomechanical stress. Increasing evidence supports the hypothesis that biomechanical stress, together with inflammatory triggers such as antigens and changes in the microbiome, can contribute to the onset of PsA and SpA by inducing local microdamage in the entheses. Objectives Here, we aim to understand early events leading to PsA and SpA by combining a protocol of forced exercise in mice with simultaneous locally-induced cutaneous or intestinal inflammation. Methods Forty 8 weeks old C57/Bl6 male mice were used to induce the PsO- or IBD-like disease, respectively by serial applications of imiquimod cream (IMQ) on a shaved area of the back skin, and administration to the intestine of dextran sodium sulphate (DSS) dissolved in drinking water. Forty control mice were left untreated. After induction of inflammation, we applied a protocol of forced treadmill running to increase biomechanical stress in half of the mice. Control mice with or without IMQ or DSS treatment did not run. We evaluated skin and gut disease severity clinically and by histology, and performed microCT scans, histological and immunohistochemical analyses of the knees and the paws, to investigate eventual changes occurring in the joints. Results Clinical and histological assessment of the skin or gut confirmed successful induction of cutaneous and intestinal inflammation. The exercise protocol slightly affected the severity of the PsO- but not of the IBD-like disease in mice. In both models, disease was not confined to the target organs as systemic inflammation was demonstrated by trabecular bone loss, as indicated by microCT analyses, and by changes in spleen size. The exercise protocol did not appear to have an additional effect on these systemic disease manifestations, but it is associated with increased articular cartilage thickness and cellularity. Signs of mild joint inflammation were seen for both the IMQ and DSS models. Mild synovitis was triggered by skin and gut disease. At the entheseal level, immunohistochemical detection for CD45 +cells showed that forced exercise boosts inflammation in the presence of inflammation triggered at a distant site. Conclusions Induction of PsO- or IBD-like inflammation by local treatments of immune-privileged barrier tissues, such as skin and gut, also triggers a systemic response with inflammation-associated bone loss and discrete signs of joint disease. Forced running exercise increased the degree of enthesitis in this setting, providing new support for the hypothesis that biomechanical stress contributes to disease manifestations in PsA and other forms of spondyloarthritis. Disclosure of Interest None declared