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

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., 5-Feb-2019, In : Cell metabolism. 29, 2, p. 348-+ 20 p.

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

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DOI

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

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.

Original languageEnglish
Pages (from-to)348-+
Number of pages20
JournalCell metabolism
Volume29
Issue number2
Early online date2018
Publication statusPublished - 5-Feb-2019

    Keywords

  • INSULINOMA-RELEASED EXOSOMES, NOD MOUSE MODEL, EXTRACELLULAR VESICLES, GENE-EXPRESSION, ALPHA CELLS, T-CELLS, IN-VIVO, KAPPA-B, INSULITIS, RNAS

ID: 66758433