Natural Aryl Hydrocarbon Receptor Ligands Control Organogenesis of Intestinal Lymphoid Follicles

Innate lymphoid cells (ILC) expressing the transcription factor ROR gamma t induce the postnatal formation of intestinal lymphoid follicles and regulate intestinal homeostasis. ROR gamma t(+) ILC express the aryl hydrocarbon receptor (AhR), a highly conserved, ligand-inducible transcription factor believed to control adaptation of multicellular organisms to environmental challenges. We show that AhR is required for the postnatal expansion of intestinal ROR gamma t(+) ILC and the formation of intestinal lymphoid follicles. AhR activity within ROR gamma t(+) ILC could be induced by dietary ligands such as those contained in vegetables of the family Brassicaceae. AhR-deficient mice were highly susceptible to infection with Citrobacter rodentium, a mouse model for attaching and effacing infections. Our results establish a molecular link between nutrients and the formation of immune system components required to maintain intestinal homeostasis and resistance to infections.