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Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity.

Nat Commun. 2020 Jul 24;11(1):3755
Amine Toubal 1 , Badr Kiaf 2 , Lucie Beaudoin 2 , Lucie Cagninacci 2 , Moez Rhimi 3 , Blandine Fruchet 4 , Jennifer da Silva 4 , Alexandra J Corbett 5 , Yannick Simoni 2 , Olivier Lantz 6 , Jamie Rossjohn 7 , James McCluskey 5 , Philippe Lesnik 8 , Emmanuelle Maguin 3 , Agnès Lehuen 9
Amine Toubal 1 , Badr Kiaf 2 , Lucie Beaudoin 2 , Lucie Cagninacci 2 , Moez Rhimi 3 , Blandine Fruchet 4 , Jennifer da Silva 4 , Alexandra J Corbett 5 , Yannick Simoni 2 , Olivier Lantz 6 , Jamie Rossjohn 7 , James McCluskey 5 , Philippe Lesnik 8 , Emmanuelle Maguin 3 , Agnès Lehuen 9
+ et al

[No authors listed]

Author information
  • 1 Laboratoire d'Excellence INFLAMEX, Sorbonne Paris Cité, Paris, France. aminetoubal@gmail.com.
  • 2 Laboratoire d'Excellence INFLAMEX, Sorbonne Paris Cité, Paris, France.
  • 3 INRA Micalis Institute, Jouy-en-Josas, Paris, France.
  • 4 Université de Paris, Institut Cochin INSERM, CNRS F-75014, Paris, France.
  • 5 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
  • 6 INSERM U932, Institut Curie, PSL University, Paris, France.
  • 7 Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
  • 8 Institute of Cardiometabolism and Nutrition, ICAN, INSERM, 1166, Paris, France.
  • 9 Laboratoire d'Excellence INFLAMEX, Sorbonne Paris Cité, Paris, France. agnes.lehuen@inserm.fr.

摘要

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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