Aryl hydrocarbon receptor: An environmental sensor in control of allergy outcomes

Abstract

The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AhR) has immune-modulating functions and responds to a wide variety of small molecules. Since AhR is highly expressed in cells at body surfaces, such as skin, gut mucosa and particularly in mucosal-associated lymphocytes, this molecule is perfectly positioned to be a sensor of external environmental signals. The role of AhR in the balance of immunity and tolerance and in the control of local homeostasis has been clearly demonstrated in recent years [Kiss et al., Science (New York, NY) 334(6062):1561–1565, 2011; Li et al., Cell 147(3):629–640, 2011]. Deletion of AhR in mice resulted in altered composition of gut microbiota, impaired function and inflammatory immune activation of gut epithelium. In addition to xenobiotics, AhR ligands now include endogenous metabolites, dietary derivatives and bacterial metabolites (Denison and Nagy. Annu Rev Pharmacol Toxicol 43:309–334, 2003). Xenobiotics such as dietary components, products of microbiota, and ubiquitous environmental pollutants may have shaped the AhR system in intestinal epithelia or other body surfaces during millions of years of evolution. Thus, the crosstalk among the dietary components/xenobiotics, AhR and the gut microbiome appears to be an important factor in the maintenance of the mucosal immunity and immune homeostasis. These exciting discoveries provide a novel perspective for the biological role of AhR, which has been originally studied only as a sensor of toxicants, but which has been now implicated in a wide range of human conditions, including autoimmune and allergic disorders.