Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-defensin 14 Expression in Pancreatic Endocrine Cells Preventing Autoimmune Diabetes - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cell Metabolism Année : 2018

Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-defensin 14 Expression in Pancreatic Endocrine Cells Preventing Autoimmune Diabetes

Patrick Emond

Résumé

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 prevents autoimmunity in distant organs remains poorly defined. Here we reveal that gut microbiota conditioned innate lymphoid cells (ILCs) induce the expression of mouse β-defensin 14 (mBD14) by pancreatic endocrine cells, preventing autoimmune diabetes in the non-obese diabetic (NOD) mice. MBD14 stimulates, via Toll-like receptor 2, interleukin-4 (IL-4)-secreting B cells that induce regulatory macrophages, which in turn induce protective regulatory T cells. The gut microbiota-derived molecules, aryl hydrocarbon receptor (AHR) ligands and butyrate, promote IL-22 secretion by pancreatic ILCs, which induce expression of mBD14 by endocrine cells. Dysbiotic microbiota and low-affinity AHR allele explain the defective pancreatic expression of mBD14 observed in NOD mice. Our study reveals a yet unidentified crosstalk between ILCs and endocrine cells in the pancreas that is essential for the prevention of autoimmune diabetes development.

Domaines

Immunité innée
Fichier principal
Vignette du fichier
DIANA_Julien.pdf (7.45 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01907399 , version 1 (29-10-2018)

Identifiants

Citer

Michela Miani, Julie Le Naour, Emmanuelle Waeckel-Enée, Subash Chand Verma, Marjolene Straube, et al.. Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-defensin 14 Expression in Pancreatic Endocrine Cells Preventing Autoimmune Diabetes. Cell Metabolism, 2018, 28 (4), pp.557 - 572.e6. ⟨10.1016/j.cmet.2018.06.012⟩. ⟨hal-01907399⟩
337 Consultations
178 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More