Mend Your Fences

Abstract

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.

Inhibition of phosphodiesterase‐4 attenuates murine ulcerative colitis through interference with mucosal immunity

“…The intestinal mucosal barrier plays an essential role in protecting homeostasis against the chaotic invasion of many antigens from the external environment (Martini, Krug, Siegmund, Neurath, & Becker, 2017;Turner, 2009). Genome-wide association studies have identified several UC-susceptible genes involved in intestinal barrier function, including HNF4, CDH1, and LAMB1 (Oshima & Miwa, 2016).…”

Occludin knockdown is not sufficient to induce transepithelial macromolecule passage

“…3,4 A basal paracellular passage pathway is assumed to exist for larger solutes (>4 Å), 1,5 and this leak pathway is believed to be dysregulated in diseases such as inflammatory bowel disease (IBD) or celiac disease (CD), or possibly even to contribute to their induction. 3,[6][7][8] It has been a long-standing issue to get behind the cellular and molecular mechanisms of the leak pathway with occludin, as one of the tight junction proteins, being suggested to regulate it. [9][10][11][12][13][14][15] Partly on this account, occludin is considered a key marker of epithelial barrier function.…”

Gamma-glutamyltranspeptidase expression byHelicobacter saguini, an enterohepaticHelicobacterspecies isolated from cotton top tamarins with chronic colitis

“…Our in vitro findings suggest the antiproliferative effects of HSGGT1 to colon epithelial cells could contribute to the deterioration of intestinal barrier integrity. Impaired barrier function is a defining characteristic of IBD, and it is hypothesised to initiate and promote unregulated and sustained proinflammatory responses by allowing excessive penetration of luminal bacteria and foreign antigens into the lamina propria (Abraham & Cho, 2009;Martini, Krug, Siegmund, Neurath, & Becker, 2017;Thoreson & Cullen, 2007;Xavier & Podolsky, 2007 In conclusion, we have shown H. saguini expresses an enzymatically active GGT homologue with potential virulence properties. Gibco/Thermo Fisher Scientific, Grand Island, NY) at 37°C with 5% CO 2 .…”