title: The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells.
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 adult but 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.
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Qiu
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Heller
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Guo
authors.forename: Zong-ming E
authors.initials: ZM
authors.lastname: Chen
authors.forename: Kamonwan
authors.initials: K
authors.lastname: Fish
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000502:physiology; D004756:Enterobacteriaceae Infections / Q000276:immunology; D041981:Gastrointestinal Tract / Q000276:immunology*; D017353:Gene Deletion; D007113:Immunity, Innate; D007378:Interleukins / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D000097043:Interleukin-22