Inter- and intra-epithelial regulation for intestinal barrier integrity

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The intestinal epithelium forms the first line of defense against bacterial invasion while providing a proper microenvironment to support microbial symbiosis. The diverse functions of intestinal epithelial cells have been demonstrated to play distinct roles in modulating the homeostatic host-microbial interactions for tissue physiology. The integrity of this barrier is crucial for preventing the entry of harmful pathogens and toxins from the gut into the bloodstream. The regulation of intestinal barrier integrity involves both inter- and intra-epithelial mechanisms. Dysregulation of these mechanisms can lead to increased intestinal permeability, inflammation, and a range of gastrointestinal diseases. Moreover, IECs function as one major component to compromise the intestinal barrier, facilitating the establishment of an immunological interface to support commensal bacteria colonization while protecting tissue from pathogen invasion. We demonstrate that autophagy in goblet cells plays a critical role in establishing commensalism and maintaining intestinal barrier integrity. Further, our work suggests that goblet cell-mediated protein sialyation is crucial for intestinal mucus integrity and host-microbial homeostasis5. Thus, understanding inter- and intra-epithelial regulation and the interactions between the gut microbiome and the host can shed light on the pathogenesis of intestinal inflammation and provide new avenues for disease intervention and treatment.