Journal
CELL METABOLISM
Volume 29, Issue 2, Pages 348-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2018.09.011
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Funding
- Swiss National Science Foundation [31003A-127254]
- European Foundation for the Study of Diabetes
- Fondation Romande pour la recherche sur le diabete
- Novartis Foundation for Medical-Biological Research
- Dutch Diabetes Foundation
- Foundation of the Beatrix Children's Hospital
- Fondation pour la Recherche Medicale [FRM-2010]
- European Union - Project PEVNET [261441]
- Italian Ministry of Research [2015373Z39_007]
- Fondazione Roma
- Fonds de Recherche du Quebec-Sante
- Canadian Diabetes Association
- Societe Francophone du Diabete
- SNF Ambizione [PZ00P3_161459]
- Swiss National Science Foundation (SNF) [31003A_127254, PZ00P3_161459] Funding Source: Swiss National Science Foundation (SNF)
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Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the beta 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 beta cells favoring apoptosis. Inactivation of these miRNAs in recipient beta 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 beta cells. The induction of these genes may promote the recruitment of immune cells and exacerbate beta 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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