Intestinal Immune Homeostasis and Inflammatory Bowel Disease: A Perspective on Intracellular Response Mechanisms

Abstract

The pathogenesis of inflammatory bowel disease (IBD) involves perturbation of intestinal immune homeostasis in genetically susceptible individuals. A mutual interplay between intestinal epithelial cells (IECs) and gut resident microbes maintains a homeostatic environment across the gut. An idiopathic gastrointestinal (GI) complication triggers aberrant physiological stress in the epithelium and peripheral myeloid cells, leading to a chronic inflammatory condition. Indeed, events in the endoplasmic reticulum (ER) and mitochondria contribute to orchestrating intracellular mechanisms such as the unfolded protein response (UPR) and oxidative stress, respectively, to resolve aberrant cellular stress. This review highlights the signaling cascades encrypted within ER and mitochondria in IECs and/or myeloid cells to dissipate chronic stress in maintaining intestinal homeostasis.