The Aryl Hydrocarbon Receptor Regulates Gut Immunity through Modulation of Innate Lymphoid Cells

Ju Qiu, Jennifer J. Heller, Xiaohuan Guo, Zong Ming E Chen, Kamonwan Fish, Yang Xin Fu, Liang Zhou

Research output: Contribution to journalArticle

367 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)92-104
Number of pages13
JournalImmunity
Volume36
Issue number1
DOIs
StatePublished - Jan 27 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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