Immune cell-derived signals governing epithelial phenotypes in homeostasis and inflammation

Inflammatory mediators have context-dependent pro- and anti-repair effects on the intestinal epithelium.Inflammatory pro-repair effects might be impaired by anti-inflammatory therapies against inflammatory bowel disease (IBD).A detailed understanding of epithelial integration of inflammatory signals and their translation into repair responses might inform novel, more targeted treatment strategies to boost epithelial repair and promote mucosal healing in IBD. The intestinal epithelium fulfills important physiological functions and forms a physical barrier to the intestinal lumen. Barrier function is regulated by several pathways, and its impairment contributes to the pathogenesis of inflammatory bowel disease (IBD), a chronic inflammatory condition affecting more than seven million people worldwide. Current treatment options specifically target inflammatory mediators and have led to improvement of clinical outcomes; however, a significant proportion of patients experience treatment failure. Pro-repair effects of inflammatory mediators on the epithelium are emerging. In this review we summarize current knowledge on involved epithelial pathways, identify open questions, and put recent findings into clinical perspective, and pro-repair effects. A detailed understanding of epithelial pathways integrating mucosal stimuli in homeostasis and inflammation is crucial for the development of novel, more targeted therapies. The intestinal epithelium fulfills important physiological functions and forms a physical barrier to the intestinal lumen. Barrier function is regulated by several pathways, and its impairment contributes to the pathogenesis of inflammatory bowel disease (IBD), a chronic inflammatory condition affecting more than seven million people worldwide. Current treatment options specifically target inflammatory mediators and have led to improvement of clinical outcomes; however, a significant proportion of patients experience treatment failure. Pro-repair effects of inflammatory mediators on the epithelium are emerging. In this review we summarize current knowledge on involved epithelial pathways, identify open questions, and put recent findings into clinical perspective. A detailed understanding of epithelial pathways integrating mucosal stimuli in homeostasis and inflammation is crucial for the development of novel, more targeted therapies.