Role of Epithelial Cells in Inflammatory Bowel Disease

Abstract

A single layer of intestinal epithelial cells (IECs) forms the barrier between the largest accumulation of microbes in the body and the host itself. Functional insight into the biology of IECs has revealed a profound impact of IEC function on mucosal homeostasis and immune function. Moreover, genome-wide association studies and candidate gene studies have substantially expanded our insight into the genetic underpinning of human inflammatory bowel disease. Several pathways regulated by products of genes that are genetically associated with inflammatory bowel disease, like the endoplasmic stress response (XBP1), autophagy (ATG16L1), and innate immune pathways (NOD2) profoundly affect IEC function, in particular Paneth cells. Paneth cells reside at the base of small intestinal crypts and secrete abundant amounts of antimicrobial peptides, and are thereby considered to substantially affect the composition of the microbial flora. Further evidence from the study of NFκB signaling in IECs revealed important insights into how IECs regulate mucosal innate and adaptive immunity via cross-talk with dendritic cells, macrophages and CD4+ T cells. These studies indicate that IECs may play a profound role in regulating the interaction between commensal and infectious microbes of the intestinal tract and the host, with consequent implications for infectious and inflammatory diseases of the gastrointestinal tract.