Intestinal Autophagy and Its Pharmacological Control in Inflammatory Bowel Disease

Abstract

Intestinal mucosal barrier, mainly composed of the intestinal mucus layer and the epithelium, plays a critical role in nutrient absorption as well as protection from pathogenic microorganisms. It is widely acknowledged that the damage of intestinal mucosal barrier or the disturbance of microorganism balance in the intestinal tract contributes greatly to the pathogenesis and progression of inflammatory bowel disease (IBD), which mainly includes Crohn's disease and ulcerative colitis. Autophagy is an evolutionarily conserved catabolic process that involves degradation of protein aggregates and damaged organelles for recycling. The roles of autophagy in the pathogenesis and progression of IBD have been increasingly studied. This present review mainly describes the roles of autophagy of Paneth cells, macrophages, and goblet cells in IBD, and finally, several potential therapeutic strategies for IBD taking advantage of autophagy.

Keywords: Paneth cell; autophagy; goblet cell; immune reaction; inflammatory bowel disease; macrophage.

Figure 1

Schematic illustration of impact of autophagy in Paneth cells, macrophages, and goblet cells in IBD. Under the exposure of DAMPs or PAMPs, autophagy process is induced in Paneth cells, macrophages, and goblet cells in the gut wall. (A) Autophagy in Paneth cells triggers the formation of functional granules and substantial release of the AMPs. In addition, autophagy suppresses pro-inflammatory cytokines secreted by Paneth cells. (B) In macrophages, autophagy promotes the degradation of pathogens and the presentation of antigens. Autophagy also inhibits the secretion of pro-inflammatory cytokines by macrophages. (C) In goblet cells, autophagy promotes the formation of mucins granules and secretion of mucins. IBD, inflammatory bowel disease; DAMPs, damage-associated molecular pattern molecules; PAMPs, pathogen- associated molecular patterns; AMPs, antimicrobial peptides.

Figure 2

Schematic illustration of the impact of autophagy on NLRP3 inflammasome. Autophagy inducers promote autophagy process which inhibits the formation of NLRP3 inflammasome (integrated by NLRP3, ASC, and pro-caspase-1), thus suppressing the activation of caspase-1 and subsequent production of IL-1β. NLRP3, NLR family, pyrin domain-containing 3; ASC, adapter protein apoptosis-associated speck-like protein; IL-1β, interleukin-1β.