Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.

Abstract

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract. Autophagy, an essential intracellular homeostatic process, plays a pivotal role in the pathogenesis and progression of IBD. This review systematically examines recent advances in understanding the involvement of autophagy in IBD, with a particular focus on the regulatory mechanisms governing its sequential phases-initiation, elongation, and termination-and their respective contributions to intestinal inflammation. We highlight how dysregulation of core autophagy components, including the ULK1 complex, Beclin 1 complex, and ATG16L1, influences inflammatory responses. Furthermore, this article delves into the context-dependent roles of selective autophagy pathways such as mitophagy, ER-phagy, and xenophagy in IBD, as well as the emerging significance of non-autophagic functions exerted by autophagy-related genes. By integrating these multifaceted aspects, this review aims to provide a theoretical foundation and identify potential targets for future precision therapeutics targeting autophagy in IBD.