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MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORγt⁺ T cells.

Authors
  • Ohnmacht, Caspar1
  • Park, Joo-Hong1
  • Cording, Sascha1
  • Wing, James B2
  • Atarashi, Koji3
  • Obata, Yuuki4
  • Gaboriau-Routhiau, Valérie5
  • Marques, Rute1
  • Dulauroy, Sophie1
  • Fedoseeva, Maria6
  • Busslinger, Meinrad7
  • Cerf-Bensussan, Nadine8
  • Boneca, Ivo G9
  • Voehringer, David10
  • Hase, Koji4
  • Honda, Kenya11
  • Sakaguchi, Shimon12
  • Eberl, Gérard13
  • 1 Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France. , (France)
  • 2 Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. , (Japan)
  • 3 RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan. , (Japan)
  • 4 The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. , (Japan)
  • 5 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. , (France)
  • 6 Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Munich, Germany. , (Germany)
  • 7 Research Institute of Molecular Pathology, Vienna Biocenter, 1030 Vienna, Austria. , (Austria)
  • 8 INSERM, U1163, Laboratory of Intestinal Immunity, Paris, France. Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, Paris, France. , (France)
  • 9 Institut Pasteur, Biology and Genetics of Bacterial Cell Wall, 75724 Paris, France. INSERM, Groupe Avenir, 75015 Paris, France. , (France)
  • 10 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. , (Germany)
  • 11 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. , (Japan)
  • 12 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. , (Japan)
  • 13 Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France. [email protected] , (France)
Type
Published Article
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Aug 28, 2015
Volume
349
Issue
6251
Pages
989–993
Identifiers
DOI: 10.1126/science.aac4263
PMID: 26160380
Source
Medline
License
Unknown

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.

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