P041 C-jun n-terminal kinase 2 promotes enterocyte survival and goblet cell differentiation in the inflamed intestine

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Background: c-Jun N-terminal kinases (JNKs) contribute to immune signalling but their functional role during intestinal mucosal inflammation has remained ill defined

Methods: Using genetic mouse models we characterized the role of JNK1 and JNK2 during homeostasis and acute colitis. Epithelial apoptosis, regeneration, differentiation and barrier function were analysed in intestinal epithelium-specific (ΔIEC) or complete JNK1 and bone-marrow chimeric or complete JNK2 deficient mice as well as double knockout animals (JNK1ΔIECJNK2−/−) during homeostasis and acute dextran sulfate sodium (DSS)-induced colitis. Results were confirmed using human HT-29 cells and wildtype (WT) or JNK2 deficient mouse intestinal organoid cultures.

Results: We show that non-hematopoetic JNK2 but not JNK1 expression confers protection from DSS-induced intestinal inflammation reducing epithelial barrier dysfunction and enterocyte apoptosis. JNK2 additionally enhanced Atonal homolog 1 (Atoh1) expression, goblet cell and enteroendocrine cells differentiation and mucus production under inflammatory conditions.

Conclusions: Our results identify a protective role of epithelial JNK2 signalling to maintain mucosal barrier function, epithelial cell integrity and mucus layer production in the event of inflammatory tissue damage.

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