Innate lymphoid cells (ILCs) expressing the nuclear receptor RORγt are essential for gut immunity presumably through production of interleukin-22 (IL-22). The molecular mechanism underlying the development of RORγt + ILCs is poorly understood. Here, we have shown that the aryl hydrocarbon receptor (Ahr) plays an essential role in RORγt + ILC maintenance and function. Expression of Ahr in the hematopoietic compartment was important for accumulation of adultbut not fetal intestinal RORγt + ILCs. Without Ahr, RORγt + ILCs had increased apoptosis and less production of IL-22. RORγt interacted with Ahr and promoted Ahr binding at the Il22 locus. Upon IL-23 stimulation, Ahr-deficient RORγt + ILCs had reduced IL-22 expression, consistent with downregulation of IL-23R in those cells. Ahr-deficient mice succumbed to Citrobacter rodentium infection, whereas ectopic expression of IL-22 protected animals from early mortality. Our data uncover a previously unrecognized physiological role for Ahr in promoting innate gut immunity by regulating RORγt + ILCs.
|Original language||English (US)|
|Number of pages||13|
|State||Published - Jan 27 2012|
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases