title: AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch.
abstract: Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in ILC22 cells that resulted in less secretion of IL-22 and inadequate protection against intestinal bacterial infection. Ahr(-/-) mice also lacked postnatally 'imprinted' cryptopatches and isolated lymphoid follicles (ILFs), but not embryonically 'imprinted' Peyer's patches. AHR induced the transcription factor Notch, which was required for NKp46(+) ILCs, whereas LTi-like ILCs, cryptopatches and ILFs were partially dependent on Notch signaling. Thus, AHR was essential for ILC22 cells and postnatal intestinal lymphoid tissues. Moreover, ILC22 subsets were heterogeneous in their requirement for Notch and their effect on the generation of intestinal lymphoid tissues.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Lee
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.forename: Keely G
authors.initials: KG
authors.lastname: McDonald
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kennedy
authors.forename: Manabu
authors.initials: M
authors.lastname: Nukaya
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Raphael
authors.initials: R
authors.lastname: Kopan
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bradfield
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism*; D051883:Receptor, Notch2 / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D000950:Antigens, Ly; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D018336:Receptors, Aryl Hydrocarbon; D000097043:Interleukin-22; C118384:Ncr1 protein, mouse; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse
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