Intestinal mucosal barrier function in health and disease

Mucosal barrier function consists of the combined effects of multiple extracellular and cellular processes that may be disrupted globally or in a targeted manner by physiological and pathophysiological stimuli. In the presence of an intact epithelium, mucosal permeability is primarily determined by tight junction barrier function.Intestinal epithelial cells mediate interactions between the mucosal immune system and luminal materials. The mechanisms by which these epithelia regulate and, conversely, are regulated by the immune system are therefore of crucial importance to mucosal homeostasis and disease.In vitro and in vivo studies have indicated that cytokines, including tumour necrosis factor, LIGHT (also known as TNFSF14), interferon-γ, interleukin-13 (IL-13) and IL-17 can modify epithelial barrier function by mechanisms that include new protein synthesis, membrane trafficking, kinase activation, cytoskeletal modulation and epithelial apoptosis. The contributions of these events to acute and chronic barrier regulation are distinct and may complement one another.Increased intestinal permeability is associated with inflammatory bowel disease but can also be present in healthy individuals. Mouse models confirm that intestinal barrier dysregulation alone is insufficient to cause disease, but they also show that enhanced tight junction permeability can accelerate disease onset and increase severity.In addition to activating pro-inflammatory events, intestinal barrier dysfunction initiates immunoregulatory processes. Defects in these processes may be a cause of inflammatory disease.Further investigation of pathways that integrate mucosal barrier function, or dysfunction, and immune regulation will lead to a better understanding of the mechanisms underlying these complex interactions and provide a rational basis for the development of more effective and targeted therapeutic interventions.