The aryl hydrocarbon receptor

Large numbers of intra-epithelial lymphocytes (IELs) intercalate between epithelial cells in the intestine and play a key role in resistance to infection and maintenance of homeostasis. In mice, expression of the aryl hydrocarbon receptor (AhR) on IELs is required for their long-term maintenance in the intestinal epithelium, independent of other AhR-expressing cell types. AhR can be activated by hydrocarbon compounds from cruciferous vegetables such as broccoli, cabbage and cauliflower. AhR knockout mice and mice reared on diets lacking AhR ligands are more susceptible to infection and epithelial injury than wild-type mice, and mice lacking AhR may suffer from premature death depending on the environment. This provides a striking example of how bioactive compounds in food can influence immunity and organismal health. AhR may be an interesting target for therapeutic intervention in inflammatory diseases or the development of the mucosal immune system in early life. However, this requires more knowledge of how AhR affects the function of IELs in the human gut, which is the goal of this project. Furthermore, the goal to identify novel sources of AhR ligands in food, milk and metabolites produced by microbiota will open up exciting possibilities for immunomodulation using novel microbes or nutrition.