Organ-specific protection mediated by cooperation between vascular and epithelial barriers

The classical concept of immune privilege as an exclusion of immune cells has been extended to include sites of immune tolerance induction, such as the intestine.Barriers can be grouped into three main categories: first, protective barriers consisting of tightly regulated endothelial layers, such as the blood–brain barrier and the inner blood–retinal barrier; second, more permissive endothelial layers, such as the gut–vascular barrier; and third, immunomodulatory selective epithelial gateways, such as the blood–cerebrospinal fluid barrier, intestinal epithelial barrier and outer blood–retinal barrier.The intestinal microbiota can influence the functionality of not only proximal intestinal barriers but also other vascular barriers that are present at distant sites, such as the brain, eye and testis.Disruption of intestinal barriers and leakage of bacteria and/or bacterial metabolites can lead to the failure of other barriers at distant sites and the development of various neurological, metabolic and intestinal disorders.