The tight junctions (TJ) present between intestinal epithelial cells act as a paracellular barrier and serve as a first line of defense against permeation of noxious antigens present in the intestinal lumen. Defective intestinal tight junction (TJ) barrier allows penetration of harmful luminal antigens in the gut which in turn leads to intestinal inflammation. Autophagy is a normal process that helps cell survival by recycling the nutrients and energy via degradation and turnover of the misfolded or unnecessary proteins. Recent studies have shown that mutations in autophagy related genes and defects in autophagy process are risk factors for inflammatory bowel disease (IBD) including Crohn disease (CD). The purpose of this grant application is to elucidate the mechanisms involved in autophagy-mediated enhancement of the intestinal epithelial tight junction barrier. Clinically, maintenance of mucosal barrier in the intestine is critical for the prevention of intestinal mucosal damage and therapeutic success in IBD cases. This study will provide novel insights into the crucial role of autophagy in enhancement of intestinal barrier and prevention of intestinal inflammation.