Mend Your Fences: The Epithelial Barrier and its Relationship With Mucosal Immunity in Inflammatory Bowel Disease

Cell Mol Gastroenterol Hepatol. 2017 Mar 23;4(1):33-46. doi: 10.1016/j.jcmgh.2017.03.007. eCollection 2017 Jul.


The intestinal epithelium can be easily disrupted during gut inflammation as seen in inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease. For a long time, research into the pathophysiology of IBD has been focused on immune cell-mediated mechanisms. Recent evidence, however, suggests that the intestinal epithelium might play a major role in the development and perpetuation of IBD. It is now clear that IBD can be triggered by disturbances in epithelial barrier integrity via dysfunctions in intestinal epithelial cell-intrinsic molecular circuits that control the homeostasis, renewal, and repair of intestinal epithelial cells. The intestinal epithelium in the healthy individual represents a semi-permeable physical barrier shielding the interior of the body from invasions of pathogens on the one hand and allowing selective passage of nutrients on the other hand. However, the intestinal epithelium must be considered much more than a simple physical barrier. Instead, the epithelium is a highly dynamic tissue that responds to a plenitude of signals including the intestinal microbiota and signals from the immune system. This epithelial response to these signals regulates barrier function, the composition of the microbiota, and mucosal immune homeostasis within the lamina propria. The epithelium can thus be regarded as a translator between the microbiota and the immune system and aberrant signal transduction between the epithelium and adjacent immune cells might promote immune dysregulation in IBD. This review summarizes the important cellular and molecular barrier components of the intestinal epithelium and emphasizes the mechanisms leading to barrier dysfunction during intestinal inflammation.

Keywords: BMP, bone morphogenic protein; CD, Crohn's disease; Fz, frizzled; HD, humans α-defensin; IBD, inflammatory bowel disease; IECs, intestinal epithelial cells; IL, interleukin; Immune-Epithelial Crosstalk; Intestinal Epithelial Barrier; Intestinal Inflammation; JAMs, junctional adhesion molecules; Lgr5, leucine rich repeat containing G-protein coupled receptor 5; MARVEL, myelin and lymphocyte and related proteins for vesicle trafficking and membrane link; MLCK, myosin light chain kinase; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; NOD-2, nucleotide-binding oligomerization domain-containing protein 2; STAT, signal transducer and activator of transcription; TAMP, tight junction–associated MARVEL protein; TJ, tight junction; TNF, tumor necrosis factor; TSLP, thymic stromal lymphopoietin; UC, ulcerative colitis.

Publication types

  • Review