Enterocytes: active cells in tolerance to food and microbial antigens in the gut

Abstract

Enterocytes used to be studied particularly in terms of digestion protagonists. However, as the immune functions of the intestinal tract were better understood, it became clear that enterocytes are not mere bystanders concerning the induction of immune tolerance to dietary peptides and gut microbiota. In fact, enterocytes are involved actively in shaping the intestinal immune environment, designed for maintaining a non-belligerent state. This tolerant milieu of the gut immune system is achieved by keeping a balance between suppression and stimulation of the inflammatory responses. Our review presents the current state of knowledge concerning the relationship between enterocytes and immune cells (dendritic cells, lymphocytes), with emphasis on the enterocytes' impact on the mechanisms leading to the induction of oral tolerance.

Fig. 1

(a) Enterocytes produce αvβ6⁺ tolerosomes, after processing food or microbial antigens. Apparently, these tolerosomes are directed to CD103⁺ dendritic cells (DCs). (b) Enterocytes participate in the translocation of secretory immunoglobulin A (sIgA) to the intestinal lumen through epithelial polymeric immunoglobulin receptor (pIgR). In the gut lumen, sIgA is involved in reducing the antigenic pressure exercised on the epithelium, helping to maintain its integrity. (c) Enterocytes produce anti-microbial peptides (AMPs) such as human β-defensin (HBD) and hepatocarcinoma–intestine–pancreas/pancreatic-associated protein (HIP/PAP), which control bacterial development in the close proximity of the mucosa, or cytokines – thymic stromal lymphopoietin (TSLP), transforming growth factor (TGF-β) – to control inflammatory responses. (d) Human enterocytes express FcRn, a receptor which facilitates the recirculation of immunoglobulin (Ig)G complexed with antigens from the gut lumen, mechanism involved in the induction of oral tolerance.