The Role of Autophagy in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn's disease (CD). The abnormality of inflammatory and immune responses in the intestine contributes to the pathogenesis and progression of IBD. Autophagy is a vital catabolic process in cells. Recent studies report that autophagy is highly involved in various kinds of diseases, especially inflammation-related diseases, such as IBD. In this review, the biological characteristics of autophagy and its role in IBD will be described and discussed based on recent literature. In addition, several therapies for IBD through modulating the inflammasome and intestinal microbiota taking advantage of autophagy regulation will be introduced. We aim to bring new insight in the exploration of mechanisms for IBD and development of novel therapeutic strategies against IBD.

Keywords: apoptosis; autophagy; inflammasome; inflammatory bowel disease; mutation.

Figure 1

Schematic illustration of the role of autophagy in IBD. The overwhelming inflammatory and immune stress in the gut contributes to the pathogenesis and progression of IBD. On the occurrence of UC, intestinal autophagy is induced and produces effects on UC via the modulation of ATF4, VDR, NRBF2, Metrnl, gut microbiota regulation, and so on. In CD, the mutation or deletion of some autophagy-related genes, including ATG16L1, IRGM, ULK-1, XBP-1, NOD2, ATG4, TCF4, and LRRK2, have been reported to be vital in the onset and development of CD. IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; ATF4, activating transcription factor 4; VDR, vitamin D receptor; NRBF2, nuclear receptor binding factor 2; ATG16L1, autophagy-related protein 16-like protein 1; IRGM, immunity-related GTPase M; ULK-1, Unc-51-like kinase-1; XBP-1, X box-binding protein 1 spliced-1; NOD2, nucleotide binding oligomerization domain containing protein 2; TCF4, transcription factor 4; LRRK2, leucine-rich repeat serine/threonine-protein kinase 2.