Lymphocyte-Derived Exosomal MicroRNAs Promote Pancreatic β Cell Death and May Contribute to Type 1 Diabetes Development.

Details

Ressource 1Download: Guay CELL METABOLISM 2019 version auteurs.pdf (2730.43 [Ko])
State: Public
Version: Author's accepted manuscript
License: Not specified
Serval ID
serval:BIB_32A6AD8B1141
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lymphocyte-Derived Exosomal MicroRNAs Promote Pancreatic β Cell Death and May Contribute to Type 1 Diabetes Development.
Journal
Cell metabolism
Author(s)
Guay C., Kruit J.K., Rome S., Menoud V., Mulder N.L., Jurdzinski A., Mancarella F., Sebastiani G., Donda A., Gonzalez B.J., Jandus C., Bouzakri K., Pinget M., Boitard C., Romero P., Dotta F., Regazzi R.
ISSN
1932-7420 (Electronic)
ISSN-L
1550-4131
Publication state
Published
Issued date
05/02/2019
Peer-reviewed
Oui
Volume
29
Number
2
Pages
348-361.e6
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the β cells. We found that rodent and human T lymphocytes release exosomes containing the microRNAs (miRNAs) miR-142-3p, miR-142-5p, and miR-155, which can be transferred in active form to β cells favoring apoptosis. Inactivation of these miRNAs in recipient β cells prevents exosome-mediated apoptosis and protects non-obese diabetic (NOD) mice from diabetes development. Islets from protected NOD mice display higher insulin levels, lower insulitis scores, and reduced inflammation. Looking at the mechanisms underlying exosome action, we found that T lymphocyte exosomes trigger apoptosis and the expression of genes involved in chemokine signaling, including Ccl2, Ccl7, and Cxcl10, exclusively in β cells. The induction of these genes may promote the recruitment of immune cells and exacerbate β cell death during the autoimmune attack. Our data point to exosomal-miRNA transfer as a communication mode between immune and insulin-secreting cells.
Keywords
Adult, Animals, Diabetes Mellitus, Type 1/metabolism, Exosomes/metabolism, Female, Humans, Insulin-Secreting Cells/cytology, Insulin-Secreting Cells/immunology, Jurkat Cells, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, MicroRNAs/physiology, Middle Aged, Rats, Rats, Wistar, T-Lymphocytes/cytology, T-Lymphocytes/immunology, T lymphocytes, cell-cell communication, exosomes, microRNAs, pancreatic β cells, type 1 diabetes
Pubmed
Web of science
Open Access
Yes
Create date
02/11/2018 16:11
Last modification date
27/04/2020 5:20
Usage data