Abstract
The intestinal epithelium represents one of our most important interfaces with the external environment. It must remain tightly balanced to allow nutrient absorption, but maintain barrier function and immune homoeostasis, a failure of which results in chronic infection or debilitating inflammatory bowel disease (IBD). The intestinal epithelium mainly consists of absorptive enterocytes and secretory goblet and Paneth cells and has recently come to light as being an essential modulator of immunity as opposed to a simple passive barrier. Each epithelial sub-type can produce specific immune modulating factors, driving innate immunity to pathogens as well as preventing autoimmunity. The enteroendocrine cells comprise just 1% of this epithelium, but collectively form the bodies' largest endocrine system. The mechanisms of enteroendocrine cell peptide secretion during feeding, metabolism and nutrient absorption are well studied; but their potential interactions with the enriched numbers of surrounding immune cells remain largely unexplored. This review focuses on alterations in enteroendocrine cell number and peptide secretion during inflammation and disease, highlighting the few in depth studies which have attempted to dissect the immune driven mechanisms that drive these phenomena. Moreover, the emerging potential of enteroendocrine cells acting as innate sensors of intestinal perturbation and secreting peptides to directly orchestrate immune cell function will be proposed. In summary, the data generated from these studies have begun to unravel a complex cross-talk between immune and enteroendocrine cells, highlighting the emerging immunoendocrine axis as a potential target for therapeutic strategies for infections and inflammatory disorders of the intestine.
Highlights
Dispersed throughout the intestinal epithelium are the enteroendocrine cells which, despite only comprising 1 % of the epithelium, collectively form the largest endocrine system in humans
Enteroendocrine cells: key orchestrators of intestinal immunity Enteroendocrine cells make up 1 % of the intestinal epithelium and, beyond their classical role of detecting luminal nutrients, they detect and respond to (1) pathogens via the expression of toll-like receptors (TLRs) and (2) the intestinal microbiome via the expression of specific receptors for the metabolites commensal bacteria produce
Enteroendocrine cells have been shown to express functional TLRs, in vitro and in vivo studies have shown that CCK-secreting cells express TLR 1, 2 and 4, with stimulation resulting in increased nuclear factor kappa light chain enhancer of activated B cells (NFκβ), mitogen-activated protein kinase (MAPK) signalling, as well as Ca flux culminating in tumour necrosis factor-α, transforming growth factor-β and macrophage inhibitory protein 2, as well as CCK release [8]
Summary
Dispersed throughout the intestinal epithelium are the enteroendocrine cells which, despite only comprising 1 % of the epithelium, collectively form the largest endocrine system in humans. Enteroendocrine cells: key orchestrators of intestinal immunity Enteroendocrine cells make up 1 % of the intestinal epithelium and, beyond their classical role of detecting luminal nutrients, they detect and respond to (1) pathogens via the expression of TLRs and (2) the intestinal microbiome via the expression of specific receptors for the metabolites commensal bacteria produce.
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