Xenobiotic and endobiotic handling by the mucosal immune system

Mucosal immune cells in the intestinal tract are continuously exposed to a barrage of both foreign and endogenously generated metabolites, termed xenobiotics, and endobiotics, respectively. This review summarizes recent insights into the mechanisms by which xenobiotics and endobiotics regulate intestinal immunity and inflammation.

The community of enteric microbes (i.e., microbiota) has profound impacts on the development and function of the mucosal immune system. The composition and function of gut microbiota is dynamically regulated by diet, and this interplay dictates which and how many immunomodulatory xenobiotics are present in the intestine. Microbiota also regulate the concentration and composition of circulating bile acids, an abundant class of liver-derived endobiotics with pleotropic immunoregulatory activities. A growing body of literature is emerging that sheds new light on the mechanisms by which xenobiotics and endobiotics interact with germline-encoded receptors and transporters to shape mucosal immune function.

The complex and dynamic interplay among xenobiotics, endobiotics, and the mucosal immune system is a new frontier in mucosal immunology that is proving fruitful for the discovery of novel and pharmacologically accessible mechanisms with relevance to human inflammatory diseases.