The mucosal barrier at a glance

Abstract

Mucosal barriers separate self from non-self and are essential for life. These barriers, which are the first line of defense against external pathogens, are formed by epithelial cells and the substances they secrete. Rather than an absolute barrier, epithelia at mucosal surfaces must allow selective paracellular flux that discriminates between solutes and water while preventing the passage of bacteria and toxins. In vertebrates, tight junctions seal the paracellular space; flux across the tight junction can occur through two distinct routes that differ in selectivity, capacity, molecular composition and regulation. Dysregulation of either pathway can accompany disease. A third, tight-junction-independent route that reflects epithelial damage can also contribute to barrier loss during disease. In this Cell Science at a Glance article and accompanying poster, we present current knowledge on the molecular components and pathways that establish this selectively permeable barrier and the interactions that lead to barrier dysfunction during disease.

Linking gut microbiota to cardiovascular disease and hypertension: Lessons from chronic kidney disease

“…The intestinal barrier is the master regulator, separating self from non-self, and coordinating all interactions between the gut microbiome and human physiology [25].…”

Targeting the gut barrier for the treatment of alcoholic liver disease

“…This selectively permeable barrier prohibits passage of microorganisms and toxins while permitting transport of nutrients and water. 33,34 The paracellular permeability of the intestinal epithelium is controlled by an apical junction complex, composed of tight junctions, adherens junctions and desmosomes, in an apical to basal orientation. The tight junction is located at the most apical position of epithelial cells, and forms the actual seal between adjacent cells.…”

Cryptosporidium parvumdisrupts intestinal epithelial barrier function via altering expression of key tight junction and adherens junction proteins

“…Intestinal epithelial barrier defects occur mostly via disruption of epithelial junctional complexes (AJC) such as tight junctions (TJ) and adherens junctions (AJ) (Guttman & Finlay, 2009; Mehta, Nijhuis, Kumagai, Lindsay, & Silver, 2015; Shen, Su, & Turner, 2009; Viswanathan et al, 2009). TJ provide the barrier required for the maintenance of the electrochemical gradients necessary for efficient transcellular ion transport (Viswanathan et al, 2009) whereas AJ serve as mechanical linkage between adjacent epithelial cells (France & Turner, 2017). These junctions comprise a variety of transmembrane proteins, coupled with cytoplasmic adaptor proteins and the actin cytoskeleton, to attach adjacent cells together thereby forming intercellular seals (France & Turner, 2017).…”