title: MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORγt⁺ T cells.
abstract: Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (T(H)17) cells and regulatory T cells (T(regs)) in the intestine. Here, we report that microbiota-induced T(regs) express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to T(H)17 cells. In the absence of RORγt(+) T(regs), T(H)2-driven defense against helminths is more efficient, whereas T(H)2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt(+) T(regs) and T(H)17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.
authors.affiliation: Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France.
authors.forename: Caspar
authors.initials: C
authors.lastname: Ohnmacht
authors.affiliation: Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France.
authors.forename: Joo-Hong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France.
authors.forename: Sascha
authors.initials: S
authors.lastname: Cording
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: James B
authors.initials: JB
authors.lastname: Wing
authors.affiliation: RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Atarashi
authors.affiliation: The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Obata
authors.affiliation: INSERM, U1163, Laboratory of Intestinal Immunity, Paris, France. Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, Paris, France. INRA Micalis UMR1319, Jouy-en-Josas, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaboriau-Routhiau
authors.affiliation: Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France.
authors.forename: Rute
authors.initials: R
authors.lastname: Marques
authors.affiliation: Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dulauroy
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Munich, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Fedoseeva
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, 1030 Vienna, Austria.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.affiliation: INSERM, U1163, Laboratory of Intestinal Immunity, Paris, France. Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.affiliation: Institut Pasteur, Biology and Genetics of Bacterial Cell Wall, 75724 Paris, France. INSERM, Groupe Avenir, 75015 Paris, France.
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.affiliation: Department of Infection Biology at the Institute of Clinical Microbiology, Immunology and Hygiene, University Clinic Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
authors.affiliation: The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.affiliation: RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. CREST, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France. gerard.eberl@pasteur.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000382:microbiology; D005856:Germ-Free Life; D006706:Homeostasis; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D018448:Models, Immunological; D009351:Nematospiroides dubius; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D017206:Strongylida Infections / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014801:Vitamin A / Q000378:metabolism
chemical_list: D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539901:Rorc protein, mouse; D014801:Vitamin A