[PDF][PDF] The gut microbiota regulates intestinal CD4 T cells expressing RORγt and controls metabolic disease

L Garidou, C Pomié, P Klopp, A Waget, J Charpentier… - Cell metabolism, 2015 - cell.com
L Garidou, C Pomié, P Klopp, A Waget, J Charpentier, M Aloulou, A Giry, M Serino…
Cell metabolism, 2015cell.com
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 …
Summary
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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