Breaking the barrier: How inflammation spreads from skin to joint

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Physical barriers of the body and their immunological dysregulation are connected to a variety of inflammatory diseases and therefore an emerging area of interest in medicine. The gut and its microbiome gained center stage, whereas the skin as large primary immunological barrier to the environment is still less appreciated. Psoriatic arthritis (PsA) is a prototypic inflammatory disease which usually starts with skin lesions, before spreading to the musculoskeletal regions. To date, it is still obscure why the inflammatory process in some patients with psoriasis is restrained to the skin, whereas in other patients it extends to tendons and joints. Moreover, disease spreading to the joints associates with local tissue remodelling as evidenced by new bone formation at the insertion site of tendons into the bones. The molecular and cellular regulation of this “skin-joint axis” leading to development of PsA is still unclear but essential to understand organ communication in inflammatory diseases, the identification of potential biomarkers for early recognition of the disease and the development of preventive treatments. We will take advantage of a new model resembling PsA, which was established in our lab, with the aim of (1) studying disease spreading from the skin to musculoskeletal regions, (2) deciphering the molecular mechanisms that lead to uncontrolled local tissue remodeling, and finally (3) testing a new translational approach to prevent spreading of inflammation and tissue remodelling. We plan to adopt cutting-edge techniques to achieve our goals, which in turn will contribute to a better knowledge of the connection between epithelial surfaces and inflammation.