Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity
Open accessAbstract
Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders.
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A stressed and unbalanced microbiota in HFD-fed obese mice decreased MAIT cell frequency by reducing MAIT cell agonist ligands, accompanied by increased gut inflammation, gut dysbiosis, and compromised gut integrity.
“a stressed and unbalanced microbiota in HFD-fed obese mice decreased MAIT cell frequency by reducing MAIT cell agonist ligands. This is accompanied by increased gut inflammation, gut dysbiosis, and compromised gut integrity.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [694]
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References 79 · Cited by 165
- Authors
- Toubal, A., Kiaf, B., Beaudoin, L., Cagninacci, L., Rhimi, M., Fruchet, B., da Silva, J., Corbett, A. J., Simoni, Y., Lantz, O., Rossjohn, J., McCluskey, J., Lesnik, P., Maguin, E., & Lehuen, A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Microbiologie de l’alimentation au service de la santé (FR)
- The University of Melbourne (AU)
- Inserm (FR)
- ARC Centre of Excellence in Advanced Molecular Imaging (AU)
- Corresponding author
- Toubal, Amine
- Lehuen, Agnès
- ORCID
- Venue
- Nature Communications
- Published
- 2020-07-24
- Volume
- 11
- Issue
- 1
- Pages
- 3755-3755
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7381641
- OpenAlex
- W3044339780
- Cited by
- 165
- References
- 79
- Citations by year
- 2026: 10 · 2025: 28 · 2024: 28 · 2023: 30 · 2022: 38 · 2021: 22 · 2020: 9
- FWCI
- 17.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- HAL (submittedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Laboratoire d'Excellence Inflamex (ANR-11-IDEX-0005-02)
- Fondation Francophone pour la Recherche sur le Diabète
- European Foundation for the Study of Diabetes
- Agence Nationale de la Recherche (ANR‐19, ANR 11 IDEX 0005-02, ANR-15-CE14, ANR-15-CE14-0029, ANR-16-CE15-0020, ANR-19-CE14, IDEX-0005, ANR-11-IDEX, ANR-10-LABX-0017, ANR-17-RHUS-0009, CE14-0029, ANR-19-CE14-0020, ANR-11-IDEX-0005, ANR-14-CE12-0018)
- Fondation pour la Recherche Médicale (EQU201903007779)
- Campus France (30666QM)
- Servier
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- mucosal-associated invariant T cells, obesity, gut dysbiosis, low-grade inflammation, insulin resistance, MR1, M1 macrophage polarization, adipose tissue inflammation, ileum, intestinal barrier integrity, glucose metabolism, lipid metabolism, metabolic dysfunction
- MeSH terms
- Gastrointestinal Microbiome, Mucosal-Associated Invariant T Cells, Adipose Tissue, Animals, Glucose Tolerance Test, Ileum, Inflammation, Intestinal Mucosa, Intestines, Ligands, Macrophages, Magnetic Resonance Imaging, Mice, Inbred C57BL, Obesity, Phenotype, Pterins, Receptors, Antigen, T-Cell, Cytokines, Lymphocyte Count, Mice, Diet, High-Fat, Dysbiosis
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