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. 2015 Jul 7;22(1):100-12.
doi: 10.1016/j.cmet.2015.06.001.

The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease

Lucile Garidou  1 , Céline Pomié  2 , Pascale Klopp  2 , Aurélie Waget  2 , Julie Charpentier  2 , Meryem Aloulou  3 , Anaïs Giry  2 , Matteo Serino  2 , Lotta Stenman  4 , Sampo Lahtinen  4 , Cedric Dray  2 , Jason S Iacovoni  5 , Michael Courtney  6 , Xavier Collet  2 , Jacques Amar  7 , Florence Servant  6 , Benjamin Lelouvier  6 , Philippe Valet  2 , Gérard Eberl  8 , Nicolas Fazilleau  3 , Victorine Douin-Echinard  2 , Christophe Heymes  2 , Rémy Burcelin  9
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Free article

The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease

Lucile Garidou et al. Cell Metab. .
Free article

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.

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