title: The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease.
abstract: A high-fat diet (HFD) induces metabolic disease and low-grade metabolic inflammation in response to changes in the intestinal microbiota through as-yet-unknown mechanisms. Here, we show that a HFD-derived ileum microbiota is responsible for a decrease in Th17 cells of the lamina propria in axenic colonized mice. The HFD also changed the expression profiles of intestinal antigen-presenting cells and their ability to generate Th17 cells in vitro. Consistent with these data, the metabolic phenotype was mimicked in RORγt-deficient mice, which lack IL17 and IL22 function, and in the adoptive transfer experiment of T cells from RORγt-deficient mice into Rag1-deficient mice. We conclude that the microbiota of the ileum regulates Th17 cell homeostasis in the small intestine and determines the outcome of metabolic disease.
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France. Electronic address: lucile.garidou@gmail.com.
authors.forename: Lucile
authors.initials: L
authors.lastname: Garidou
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Pomié
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Klopp
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Waget
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Charpentier
authors.affiliation: Université Paul Sabatier, F-31432 Toulouse, France; Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, F-31300 Toulouse, France; CNRS, UMR5282, F-31300 Toulouse, France.
authors.forename: Meryem
authors.initials: M
authors.lastname: Aloulou
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Giry
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Serino
authors.affiliation: Danisco Sweeteners Oy Sokeritehtaantie 20 FI-02460 Kantvik, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Stenman
authors.affiliation: Danisco Sweeteners Oy Sokeritehtaantie 20 FI-02460 Kantvik, Finland.
authors.forename: Sampo
authors.initials: S
authors.lastname: Lahtinen
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Dray
authors.affiliation: Plateau de Bioinformatique et Biostatistique, INSERM UMR1048, F-31432 Toulouse, France.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.affiliation: Vaiomer SAS, 516 Rue Pierre et Marie Curie, F-31670 Labège, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Courtney
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.affiliation: Université Paul Sabatier, F-31432 Toulouse, France; Hôpital Rangueil, Département Thérapeutique, F-31059 Toulouse, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Amar
authors.affiliation: Vaiomer SAS, 516 Rue Pierre et Marie Curie, F-31670 Labège, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Servant
authors.affiliation: Vaiomer SAS, 516 Rue Pierre et Marie Curie, F-31670 Labège, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lelouvier
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: Institut Pasteur, Unité de Développement des Tissus Lymphoïdes, F-75724 Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.affiliation: Université Paul Sabatier, F-31432 Toulouse, France; Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, F-31300 Toulouse, France; CNRS, UMR5282, F-31300 Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fazilleau
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Victorine
authors.initials: V
authors.lastname: Douin-Echinard
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Heymes
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France. Electronic address: remy.burcelin@inserm.fr.
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D000069196:Gastrointestinal Microbiome; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007109:Immunity; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology*; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D015704:CD4 Antigens; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3