The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease
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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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Insulin resistance caused by a high-fat diet correlates with fewer TH17 cells expressing IL-17 and RORγt.
“Insulin resistance that is induced through a high-fat diet is associated with reduced levels of T helper 17 (TH17) cells that are positive for IL-17 and retinoic acid receptor-related orphan receptor γt (RORγt)112.”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [112]
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- Authors
- Garidou, L., Pomié, C., Klopp, P., Waget, A., Charpentier, J., Aloulou, M., Giry, A., Serino, M., Stenman, L., Lahtinen, S., Dray, C., Iacovoni, J. S., Courtney, M., Collet, X., Amar, J., Servant, F., Lelouvier, B., Valet, P., Eberl, G., Fazilleau, N., Douin-Echinard, V., Heymes, C., & Burcelin, R.
- Affiliations
- Université Toulouse III - Paul Sabatier (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Corresponding author
- Garidou, Lucile
- Burcelin, Rémy
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 22
- Issue
- 1
- Pages
- 100-112
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1483529702
- Cited by
- 303
- References
- 49
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 24 · 2023: 32 · 2022: 29 · 2021: 50 · 2020: 23 · 2019: 30 · 2018: 20 · 2017: 34 · 2016: 25 · 2015: 7
- FWCI
- 12.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- gut microbiota, RORγt, Th17 cells, high-fat diet, metabolic disorders, metabolic inflammation, lamina propria, antigen-presenting cells, IL-17, IL-22, adoptive T cell therapy, Rag1-deficient mice
- MeSH terms
- Gastrointestinal Microbiome, Animals, Cells, Cultured, Diabetes Mellitus, Type 2, Gene Expression Regulation, Ileum, Immunity, Male, Obesity, CD4-Positive T-Lymphocytes, CD4 Antigens, Gene Deletion, Interleukin-17, Mice, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells, Diet, High-Fat
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