title: RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota.
abstract: Lymphoid cells that express the nuclear hormone receptor RORγt are involved in containment of the large intestinal microbiota and defense against pathogens through the production of interleukin 17 (IL-17) and IL-22. They include adaptive IL-17-producing helper T cells (T(H)17 cells), as well as innate lymphoid cells (ILCs) such as lymphoid tissue-inducer (LTi) cells and IL-22-producing NKp46+ cells. Here we show that in contrast to T(H)17 cells, both types of RORγt+ ILCs constitutively produced most of the intestinal IL-22 and that the symbiotic microbiota repressed this function through epithelial expression of IL-25. This function was greater in the absence of adaptive immunity and was fully restored and required after epithelial damage, which demonstrates a central role for RORγt+ ILCs in intestinal homeostasis. Our data identify a finely tuned equilibrium among intestinal symbionts, adaptive immunity and RORγt+ ILCs.
authors.affiliation: Institut Pasteur, Lymphoid Tissue Development Unit, Paris, France.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sawa
authors.forename: Matthias
authors.initials: M
authors.lastname: Lochner
authors.forename: Naoko
authors.initials: N
authors.lastname: Satoh-Takayama
authors.forename: Sophie
authors.initials: S
authors.lastname: Dulauroy
authors.forename: Marion
authors.initials: M
authors.lastname: Bérard
authors.forename: Melanie
authors.initials: M
authors.lastname: Kleinschek
authors.forename: Daniel
authors.initials: D
authors.lastname: Cua
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013559:Symbiosis / Q000276:immunology; D013997:Time Factors; D000097043:Interleukin-22
chemical_list: D000950:Antigens, Ly; D020381:Interleukin-17; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D000097043:Interleukin-22; C442281:Mydgf protein, mouse; C118384:Ncr1 protein, mouse