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

Guay, Claudiane; Kruit, Janine K.; Rome, Sophie; Menoud, Véronique; Mulder, Niels L.; Jurdzinski, Angelika; Mancarella, Francesca; Sebastiani, Guido; Donda, Alena; Jandus, Camilla; Bouzakri, Karim; Pinget, Michel; Boitard, Christian; Romero, Pedro; Dotta, Francesco; Regazzi, Romano

Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the b 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 b cells favoring apoptosis. Inactivation of these miRNAs in recipient b cells prevents exosome-mediated apoptosis and protects non-obese diabetic (NOD) mice from diabetes development. Is- lets 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 b cells. The induction of these genes may promote the recruitment of immune cells and exacerbate b cell death during the autoimmune attack. Our data point to exosomal-miRNA transfer as a communication mode between immune and insulin-secreting cells.

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Also Published In

Title
Cell Metabolism
DOI
https://doi.org/10.1016/j.cmet.2018.09.011

More About This Work

Academic Units
Pediatrics
Published Here
November 9, 2018