Epithelial immunity: priming defensive responses in the intestinal mucosa

Abstract

As the largest interface between the outside and internal milieu, the intestinal epithelium constitutes the first structural component facing potential luminal threats to homeostasis. This single-cell layer is the epicenter of a tightly regulated communication network between external and internal factors that converge to prime defensive responses aimed at limiting antigen penetration and the maintenance of intestinal barrier function. The defensive role developed by intestinal epithelial cells (IEC) relies largely on the variety of receptors they express at both extracellular (apical and basolateral) and intracellular compartments, and the capacity of IEC to communicate with immune and nervous systems. IEC recognize pathogen-associated molecules by innate receptors that promote the production of mucus, antimicrobial substances, and immune mediators. Epithelial cells are key to oral tolerance maintenance and also participate in adaptive immunity through the expression of immunoglobulin (Ig) receptors and by promoting local Ig class switch recombination. In IEC, different types of antigens can be sensed by multiple immune receptors that share signaling pathways to assure effective responses. Regulated defensive activity maintains intestinal homeostasis, whereas a breakdown in the control of epithelial immunity can increase the intestinal passage of luminal content and microbial invasion, leading to inflammation and tissue damage. In this review, we provide an updated overview of the type of immune receptors present in the human intestinal epithelium and the responses generated to promote effective barrier function and maintain mucosal homeostasis.

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

“…The intestinal epithelium contains a large surface that is lined by a monolayer of intestinal epithelial cells and involves diverse structural interactions among resident microbiota 150 . The intestinal epithelium is not only serves as a barrier, but has digestive, metabolic, and immune functions as well 151 . The epithelium includes specialized cells such as goblet cells that secrete mucus, Paneth cells that produce defensins, and M cells for antigen uptake 152,153 .…”

Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis

“…Extracellular luminal elements include pH, enzymes from gastric, pancreatic and biliary secretions, the mucus layer and molecules released by epithelial and immune cells, which include defensins, lisozyme, phospholipids, trefoil factor family peptides, cathelicidins, ribonucleases and Igs, mainly secretory IgA [35,36]. Furthermore, peristaltism and water and chlorine secretion into the lumen wash out content and slow down antigen translocation to the lamina propria [37]. The epithelial layer is a fundamental and multifunctional element of the barrier responsible for barrier, digestive, metabolic and immune functions [37].…”

“…Furthermore, peristaltism and water and chlorine secretion into the lumen wash out content and slow down antigen translocation to the lamina propria [37]. The epithelial layer is a fundamental and multifunctional element of the barrier responsible for barrier, digestive, metabolic and immune functions [37]. The epithelium includes specialised cells that produce and secrete mucus (goblet cells), defensins (Paneth cells), hormones and neuropeptides (enterochromaffin cells).…”

Site‐specific contribution of Toll‐like receptor 4 to intestinal homeostasis and inflammatory disease

“…The human body processes trillions of microbiological signals daily, from both external non‐self‐pathogens to internal self‐derived signs of danger (Comalada & Xaus, 2013; Pott & Hornef, 2012). Initial avoidance of infection and tissue damage is highly dependent on the evolutionary conserved innate immune system (Gribar, Richardson, Sodhi, & Hackam, 2008; Pardo‐Camacho, Gonzalez‐Castro, Rodino‐Janeiro, Pigrau, & Vicario, 2018). Unlike the adaptive immune system, the innate immune system is not specific to particular pathogens.…”