Autophagy and Apoptosis in Inflammatory Bowel Disease

Abstract

The pathogenesis of inflammatory bowel disease (IBD) implicates several interconnecting factors. Immunity and external factors interact, and most aspects are still under investigation. Autophagy and apoptosis are two critical pathways that decide the fate of the individual cells of the intestinal mucosa. Experimental and clinical data indicate that the two are closely interconnected and usually mutually exclusive. However, despite the abundant information on their role, very limited translation into therapeutic application has been seen during recent years. In this review, research on these two pathways is presented. After a general overview of autophagy and apoptosis, their association with IBD, including the important mitophagy and ferroptosis, is discussed. The influence of autophagy- and apoptosis-related genes is also discussed. Finally, the interplay of autophagy and apoptosis in IBD is presented and the implications for treatment applications are examined. It is shown that dysregulated autophagy leads to increased apoptosis of enterocytes and impairs the tight junction proteins of the protective intestinal barrier. Dysregulated autophagy also induces the downregulation of lysozyme and the other antimicrobial proteins’ production. Mucus production by the goblet cells is also reduced due to defective autophagy and increased apoptosis.