Molecular and Functional Diversity of Distinct Subpopulations of the Stressed Insulin-Secreting Cell's Vesiculome.
Animals
Apoptosis
Cell Hypoxia
Cell Line, Tumor
Cytokines
/ metabolism
DNA Damage
Dendritic Cells
/ immunology
Extracellular Vesicles
/ immunology
Female
Inflammation
/ immunology
Insulin
/ metabolism
Insulin-Secreting Cells
/ immunology
Macrophage Activation
Macrophages
/ immunology
Mice
Mice, Inbred NOD
MicroRNAs
/ metabolism
Phenotype
RAW 264.7 Cells
Secretory Pathway
Signal Transduction
Toll-like receptor
apoptotic bodies
exosomes
extracellular vesicles
microRNA
microvesicles
type 1 diabetes
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
05
2020
accepted:
07
07
2020
entrez:
26
10
2020
pubmed:
27
10
2020
medline:
20
4
2021
Statut:
epublish
Résumé
Beta cell failure and apoptosis following islet inflammation have been associated with autoimmune type 1 diabetes pathogenesis. As conveyors of biological active material, extracellular vesicles (EV) act as mediators in communication with immune effectors fostering the idea that EV from inflamed beta cells may contribute to autoimmunity. Evidence accumulates that beta exosomes promote diabetogenic responses, but relative contributions of larger vesicles as well as variations in the composition of the beta cell's vesiculome due to environmental changes have not been explored yet. Here, we made side-by-side comparisons of the phenotype and function of apoptotic bodies (AB), microvesicles (MV) and small EV (sEV) isolated from an equal amount of MIN6 beta cells exposed to inflammatory, hypoxic or genotoxic stressors. Under normal conditions, large vesicles represent 93% of the volume, but only 2% of the number of the vesicles. Our data reveal a consistently higher release of AB and sEV and to a lesser extent of MV, exclusively under inflammatory conditions commensurate with a 4-fold increase in the total volume of the vesiculome and enhanced export of immune-stimulatory material including the autoantigen insulin, microRNA, and cytokines. Whilst inflammation does not change the concentration of insulin inside the EV, specific Toll-like receptor-binding microRNA sequences preferentially partition into sEV. Exposure to inflammatory stress engenders drastic increases in the expression of monocyte chemoattractant protein 1 in all EV and of interleukin-27 solely in AB suggesting selective sorting toward EV subspecies. Functional
Identifiants
pubmed: 33101266
doi: 10.3389/fimmu.2020.01814
pmc: PMC7556286
doi:
Substances chimiques
Cytokines
0
Insulin
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1814Informations de copyright
Copyright © 2020 Giri, de Beaurepaire, Jegou, Lavy, Mosser, Dupont, Fleurisson, Dubreil, Collot, Van Endert, Bach, Mignot and Bosch.
Références
Clin Exp Immunol. 2010 May;160(2):207-14
pubmed: 20030670
Nat Rev Immunol. 2020 Apr;20(4):254-267
pubmed: 31822793
J Extracell Vesicles. 2014 Sep 08;3:
pubmed: 25279113
Biochim Biophys Acta. 1992 Feb 3;1133(3):275-85
pubmed: 1737061
Cell Rep. 2019 Dec 3;29(10):3073-3086.e5
pubmed: 31801074
Mol Cell Endocrinol. 2012 Jul 6;358(1):88-95
pubmed: 22502743
J Neuroinflammation. 2017 Jan 25;14(1):22
pubmed: 28118842
Br J Cancer. 1972 Aug;26(4):239-57
pubmed: 4561027
Eur J Immunol. 2013 Oct;43(10):2588-97
pubmed: 23817982
J Extracell Vesicles. 2019 Aug 6;8(1):1650595
pubmed: 31489147
PLoS One. 2014 Dec 12;9(12):e114868
pubmed: 25503986
Lancet. 2014 Jan 4;383(9911):69-82
pubmed: 23890997
Nat Genet. 2009 Jun;41(6):703-7
pubmed: 19430480
JAMA. 2015 Jan 6;313(1):37-44
pubmed: 25562264
Diabetologia. 2018 May;61(5):1124-1134
pubmed: 29445851
Cell Chem Biol. 2019 Apr 18;26(4):600-614.e7
pubmed: 30745238
PLoS Genet. 2017 Mar 1;13(3):e1006643
pubmed: 28248954
Trends Biochem Sci. 2016 Oct;41(10):883-892
pubmed: 27597517
Blood. 2014 Jan 9;123(2):208-16
pubmed: 24255917
Semin Cell Dev Biol. 2017 Jul;67:29-38
pubmed: 27916565
Langmuir. 2008 Dec 2;24(23):13572-80
pubmed: 18991409
Endocr Rev. 2008 May;29(3):334-50
pubmed: 18048762
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4
pubmed: 7539918
Diabetes. 2015 Apr;64(4):1329-40
pubmed: 25315007
PLoS One. 2014 Sep 09;9(9):e106153
pubmed: 25203514
Mol Cell Biol. 1996 Aug;16(8):4273-80
pubmed: 8754828
Biomaterials. 2018 Apr;162:71-81
pubmed: 29438882
Curr Diab Rep. 2019 Jul 31;19(9):69
pubmed: 31367976
Endocrinology. 1990 Jul;127(1):126-32
pubmed: 2163307
Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
pubmed: 18228490
Lancet. 2016 Jun 4;387(10035):2340-2348
pubmed: 27302273
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2110-6
pubmed: 22753494
Diabetes. 2017 Feb;66(2):460-473
pubmed: 27872147
Curr Diab Rep. 2018 Oct 6;18(11):124
pubmed: 30293191
Cell Mol Life Sci. 2008 Nov;65(23):3851-60
pubmed: 18931971
Tissue Antigens. 2003 Nov;62(5):359-77
pubmed: 14617043
Clin Immunol. 2017 Mar;176:12-22
pubmed: 28039018
Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228
pubmed: 29339798
Diabetologia. 2019 Mar;62(3):408-417
pubmed: 30483858
Am J Physiol Renal Physiol. 2019 Dec 1;317(6):F1475-F1482
pubmed: 31461349
Diabetes. 2012 Apr;61(4):954-62
pubmed: 22344559
Nat Cell Biol. 2007 Jun;9(6):654-9
pubmed: 17486113
Immunology. 2017 Jun;151(2):198-210
pubmed: 28190264
Neuron. 2014 Apr 2;82(1):47-54
pubmed: 24698267
J Am Soc Nephrol. 2018 Mar;29(3):919-935
pubmed: 29295871
Arthritis Rheumatol. 2016 May;68(5):1099-110
pubmed: 26662519
PLoS Pathog. 2015 Jul 08;11(7):e1005032
pubmed: 26154133
Endocr Rev. 2008 Feb;29(1):42-61
pubmed: 18048764
Sci Rep. 2018 Jun 12;8(1):8973
pubmed: 29895824
Cancers (Basel). 2019 Jan 24;11(2):
pubmed: 30682793
ACS Nano. 2014 Jan 28;8(1):483-494
pubmed: 24383518
Front Immunol. 2018 Jun 28;9:1486
pubmed: 30002658
Sci Rep. 2017 Jul 10;7(1):5000
pubmed: 28694505
Apoptosis. 2015 Mar;20(3):263-72
pubmed: 25604067
PLoS One. 2014 Jul 16;9(7):e102521
pubmed: 25028931
Dev Cell. 2019 Feb 25;48(4):554-572.e7
pubmed: 30745140
J Biol Chem. 2018 Oct 19;293(42):16160-16173
pubmed: 30213857
Cell Metab. 2019 Feb 5;29(2):348-361.e6
pubmed: 30318337
Endocrinology. 2018 Nov 1;159(11):3834-3847
pubmed: 30307543
Sci Rep. 2016 Nov 08;6:36162
pubmed: 27824088
Autoimmun Rev. 2016 Feb;15(2):174-83
pubmed: 26554931
Nat Neurosci. 2012 Jun;15(6):827-35
pubmed: 22610069
J Extracell Vesicles. 2013 May 27;2:
pubmed: 24009894
Cell Commun Signal. 2015 Mar 19;13:17
pubmed: 25880779
Am J Transplant. 2006 Nov;6(11):2791-5
pubmed: 16939517
Cell. 2004 Jan 23;116(2):281-97
pubmed: 14744438
Diabetes. 2002 Jan;51(1):55-65
pubmed: 11756323
Sci Rep. 2016 Apr 18;6:24436
pubmed: 27087234
J Immunol. 2011 Aug 15;187(4):1591-600
pubmed: 21734072
J Struct Biol. 1996 Jan-Feb;116(1):71-6
pubmed: 8742726
J Extracell Vesicles. 2014 Sep 18;3:
pubmed: 25317274
Exp Neurol. 2015 Jul;269:202-12
pubmed: 25917529
J Surg Res. 2003 Mar;110(1):295-303
pubmed: 12697414
Diabetes. 2012 Jul;61(7):1742-51
pubmed: 22537941
Trends Endocrinol Metab. 2011 Jul;22(7):266-74
pubmed: 21458293
J Struct Biol. 1997 Dec;120(3):343-52
pubmed: 9441937
EMBO Rep. 2006 Sep;7(9):880-5
pubmed: 16953201