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

Autor: Sophie Rome, Karim Bouzakri, Francesca Mancarella, Francesco Dotta, Bryan J. González, Christian Boitard, Romano Regazzi, Niels L. Mulder, Véronique Menoud, Alena Donda, Janine K. Kruit, Camilla Jandus, Angelika Jurdzinski, Pedro Romero, Guido Sebastiani, Claudiane Guay, Michel Pinget
Přispěvatelé: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Department of Physics [Lecce], Università del Salento [Lecce], Université de Bordeaux (UB), Department of Cell Biology and Morphology, Université de Lausanne (UNIL), University Medical Center Groningen, Partenaires INRAE, Umberto Di Mario ONLUS Foundation, University of Siena, Ludwig Center for Cancer Research, Centre Hospitalier Universitaire Vaudois (CHUV), Diabète et thérapies cellulaires, Université de Strasbourg (UNISTRA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Swiss National Science Foundation (SNSF) [31003A-127254], European Foundation for the Study of Diabetes, Fondation Romande pour la recherche sur le diabète, Novartis Foundation for Medical-Biological Research, Dutch Diabetes Foundation, Foundation of the Beatrix Children's Hospital, Fondation pour la Recherche Medicale [FRM-2010], Ministero dell' Istruzione, dell' Universita e della Ricerca (MIUR) [2015373Z39_007], Fondazione Roma, Fonds de la Recherche en Sante du Quebec, Canadian Diabetes Association, Société Francophone du Diabète, SNF Ambizione [PZ00P3_161459], European Project: 261441,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,PEVNET(2011), CarMeN, laboratoire, Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Siena = University of Siena (UNISI), ProdInra, Migration, Persistent virus infection as a cause of pathogenic inflammation in type 1 diabetes - an innovative research program of biobanks and expertise - PEVNET - - EC:FP7:HEALTH2011-01-01 - 2015-12-31 - 261441 - VALID, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Center for Liver, Digestive and Metabolic Diseases (CLDM)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Physiology
type 1 diabetes
Lymphocyte
T-Lymphocytes
[SDV]Life Sciences [q-bio]
INSULINOMA-RELEASED EXOSOMES
ALPHA CELLS
Jurkat cells
Jurkat Cells
Mice
0302 clinical medicine
Mice
Inbred NOD
Insulin-Secreting Cells
T lymphocytes
cell-cell communication
exosomes
microRNAs
pancreatic β cells
IN-VIVO
GENE-EXPRESSION
NOD mice
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Middle Aged
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
3. Good health
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Female
Beta cell
Adult
INSULITIS
KAPPA-B
Biology
pancreatic beta cells
Exosome
RNAS
03 medical and health sciences
Immune system
Correspondence
medicine
Animals
Humans
Rats
Wistar
Molecular Biology
Pancreatic islets
EXTRACELLULAR VESICLES
Cell Biology
medicine.disease
Rats
Mice
Inbred C57BL
030104 developmental biology
Diabetes Mellitus
Type 1
Diabetes Mellitus
Type 1/metabolism
Exosomes/metabolism
Insulin-Secreting Cells/cytology
Insulin-Secreting Cells/immunology
MicroRNAs/physiology
T-Lymphocytes/cytology
T-Lymphocytes/immunology
T-CELLS
Cancer research
Insulitis
030217 neurology & neurosurgery
NOD MOUSE MODEL
Zdroj: Cell Metab
Cell Metab, 2018
Cell Metabolism
Cell Metabolism, Elsevier, 2019, 29 (2), pp.348-361. ⟨10.1016/j.cmet.2018.09.011⟩
Cell Metabolism, 2019, 29 (2), pp.348-361. ⟨10.1016/j.cmet.2018.09.011⟩
Cell Mol Immunol
Cell metabolism, 29(2), 348-+. CELL PRESS
Cell metabolism, vol. 29, no. 2, pp. 348-361.e6
Cell Metabolism, Vol. 29, No 2 (2019) pp. 348-361.e6
ISSN: 1550-4131
DOI: 10.1016/j.cmet.2018.09.011⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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