Figure 2. The barrier function of the intestinal epithelium.

Distinct subpopulations of intestinal epithelial cells (IECs) are integreated into a continuous, single cell layer that is divided into apical and basolateral regions by tight juctions. Although apically expressed toll-like receptors (TLRs) are adapted to limit pro-inflammatory responses at homeostasis, there is on-going sensing of the microbiota to induce the production of anti-microbial peptides (AMPs), both by enterocytes and colonocytes of the the small and large intestine, and specialized Paneth cells in the bases of small intestinal crypts. Goblet cells produce mucin, that is organized into a dense, more highly cross-linked inner proteoglycan gel that forms an IEC-adherent inner mucous layer, and a less densely cross-linked outer mucous layer that is the result of proteolytic cleavage of the predominant intestinal mucin, MUC2. The outer layer is highly colonized by constitutents of the microbiota that attach to and degrade the complex O-linked glycans, providing short-chain fatty acids that are: toxic to potential pathogens; used by IECs as an energy source; and suppress epithelium-induced inflammation. The inner mucous layer is largely impervious to bacterial colonization or penetration, due to its high concentration of bactericidal AMPs, as well as commensal-specific secretory IgA (sIgA), which is ferried across IECs from their basolatral surface, where it is bound by the polymeric immunoglobulin receptor (pIgR), to the inner mucous layer where it is released by proteolytic cleavage of pIgR, apportion of which remins bound to sIgA. Innate lymphoid cells (ILCs), including RORγt- and AhR-expressing LTis and NK-22 cells, respond to microbiota to produce IL-22, an important stimulator of IEC AMP production and epithelial barrier integrity.