This could be either intrinsically programmed in the IECs (genetic or epigenetic) or extrinsically regulated, however, this distinction of etiology remains an open hypothetical question as currently there is little research in this area. Host factors may include changes in protein expression resulting in alterations to the epithelial barrier. In this review, we will discuss the role of the intestinal barrier and IECs in regulating food allergy, as well as specific factors (host and environmental/microbiome) that may create a susceptibility within the epithelial barrier to promote food allergy. For example, reduced expression of tight junction proteins leads to a rise in intestinal permeability associated with both local intestinal food allergies as well as systemic allergy in the form of asthma ( 11– 14). In order to achieve this the barrier maintains a hypo-reactivity to microbial ligands in stark contrast to the underlying immune-stromal-rich layer of lamina propria, which is home to the innate and adaptive immune cells with far greater reactivity to commensal and pathogenic microbial ligands ( 9, 10).ĭisruption of the integrity of the intestinal barrier is often associated with inflammatory bowel disease, however, this process is also linked to numerous other local and systemic inflammatory diseases. As the epithelium and associated mucus layer provide the first line of defense against microbes they also provide the first line of tolerance against commensal members of the microbiota. These include absorptive cells (colonocytes, enterocytes), goblet cells, enteroendocrine cells, Paneth cells (of the small intestine), tuft cells, and M cells ( 8). Each of these differentiated epithelial cell subtypes possess specific functions in maintenance of the barrier’s digestive, neuroendocrine, and immune functions. These stem cells give rise to progenitor cells (transit amplifying cells) and multiple differentiated epithelial cell subsets as they migrate through division up the crypt-villus axis before undergoing a program of apoptosis and luminal shedding. The tubular crypt and epithelial lining that defines the structure of both the small intestine and colon is continuously regenerated (every 3–5 days) by a population of long-lived Lgr5+ stem cells that reside at the base of the crypt ( 8). The intercellular junctions consist of desmosomes, gap junctions, and adherent junctions made up of various integral proteins such as claudins, occludins, and zonula occludens (ZO-1, ZO-2) which operate in concert to maintain the integrity of the epithelial barrier by regulating the paracellular transport of ions, metabolites, and macromolecules ( 4– 7). The underlying layer of intestinal epithelial cells (IECs) functions as a physical barrier facilitated by tight junctions ( 4, 5). The renewal of the mucus layer (colon consists of an inner more viscous and outer less viscous layer, small intestine a single layer only) is achieved through the secretion of mucus by goblet cells (primarily via the MUC2 gene) ( 3). It also acts to shield the host from digestive enzymes and microorganism epithelial penetration. The first layer of physical defense, the mucus layer, plays an important role in reducing adherence of pathogenic microbes while providing a rich-layer of sustenance for slow-growing anaerobic commensal organisms ( 1, 2). In order to achieve this fine balance the intestinal epithelium acts as mucosal barrier to micro-organisms while permitting a pathway to protein antigens and small molecule metabolites. The intestinal epithelium provides a controlled homeostatic system for molecular transit in order to mediate the balance of the multiple functions of the intestinal tract digestion, immunity and tolerance, and a repository for the various known and unknown symbiotic functions of the microbiota. The intestinal epithelium lining forms the luminal surface to the external environment of both the small and large intestines. Introduction to the Intestinal Epithelial Barrier
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