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Crosstalk Between Gut Microbiota, Innate Lymphoid Cells and Endocrine Cells in the Pancreas Regulates Autoimmune Diabetes

53 Pages Posted: 5 Apr 2018 Publication Status: Published

See all articles by Michela Miani

Michela Miani

University of Angers - Institut Necker-Enfants Malades

Julie Le Naour

University of Angers - Institut Necker-Enfants Malades

Subash chand Verma

University of Angers - Institut Necker-Enfants Malades

Marjolène Straube

École Normale Supérieure (ENS) - Laboratoire des BioMolécules (LBM)

Peter van Endert

University of Angers - Institut Necker-Enfants Malades

Harry Sokol

École Normale Supérieure (ENS) - Laboratoire des BioMolécules (LBM)

Julien Diana

University of Angers - Institut Necker-Enfants Malades

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Abstract

The gut microbiota is essential for the normal function of the gut immune system and microbiota alterations are associated with autoimmune disorders. However how the gut microbiota influences the immune system in distant organs to prevent autoimmunity remains poorly defined. Here we reveal that the gut microbiota stimulates innate lymphoid cells (ILCs) in the pancreas leading to the expression of the mouse β-defensin 14 (mBD14) that prevents autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Pancreatic endocrine cells constitutively express mBD14 in non-autoimmune mice but not in NOD mice. MBD14 stimulates, via TLR2, IL-4-secreting B cells that induce regulatory macrophages, which in turn induce regulatory T cells. The gut microbiota-derived molecules, AHR ligands and butyrate, promote IL-22 secretion by pancreatic type 3 ILCs that, in turn induces pancreatic expression of mBD14. Dysbiotic microbiota and low-affinity AHR allele explain the defective pancreatic expression of mBD14 in NOD mice. Our findings reveal a novel interplay between the gut microbiota and ILCs that contributes in maintaining pancreatic immune tolerance.

Suggested Citation

Miani, Michela and Naour, Julie Le and Verma, Subash chand and Straube, Marjolène and Endert, Peter van and Sokol, Harry and Diana, Julien, Crosstalk Between Gut Microbiota, Innate Lymphoid Cells and Endocrine Cells in the Pancreas Regulates Autoimmune Diabetes (2018). Available at SSRN: https://ssrn.com/abstract=3155932 or http://dx.doi.org/10.2139/ssrn.3155932
This version of the paper has not been formally peer reviewed.

Michela Miani

University of Angers - Institut Necker-Enfants Malades

Bâtiment Leriche - Etage 4
14 Rue Maria Helena Vieira da Silva
Paris, 75993
France

Julie Le Naour

University of Angers - Institut Necker-Enfants Malades

Bâtiment Leriche - Etage 4
14 Rue Maria Helena Vieira da Silva
Paris, 75993
France

Subash chand Verma

University of Angers - Institut Necker-Enfants Malades

Bâtiment Leriche - Etage 4
14 Rue Maria Helena Vieira da Silva
Paris, 75993
France

Marjolène Straube

École Normale Supérieure (ENS) - Laboratoire des BioMolécules (LBM)

24 rue Lhomond
Paris, 75005
France

Peter van Endert

University of Angers - Institut Necker-Enfants Malades

Bâtiment Leriche - Etage 4
14 Rue Maria Helena Vieira da Silva
Paris, 75993
France

Harry Sokol

École Normale Supérieure (ENS) - Laboratoire des BioMolécules (LBM)

24 rue Lhomond
Paris, 75005
France

Julien Diana (Contact Author)

University of Angers - Institut Necker-Enfants Malades ( email )

Bâtiment Leriche - Etage 4
14 Rue Maria Helena Vieira da Silva
Paris, 75993
France

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