title: Phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via MSC-derived exosomes.
abstract: Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes' membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes.
authors: Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;
authors: Aram
authors: A
authors: Mokarizadeh
authors: Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;
authors: Nowruz
authors: N
authors: Delirezh
authors: Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;
authors: Ahhmad
authors: A
authors: Morshedi
authors: Department of Immunology and Microbiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran;
authors: Ghasem
authors: G
authors: Mosayebi
authors: Department of Pathobiology and Electron Microscope Center, Urmia University, Urmia, Iran;
authors: Amir-Abbas
authors: AA
authors: Farshid
authors: Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors: Bahram
authors: B
authors: Dalir-Naghadeh
keywords: Auto-reactive cell; EAE; Exosome; MSC; Tolerogenic molecule
references: Clin Exp Immunol. 2010 Oct;162(1):1-11
references: 20682002
references: J Immunol. 2003 May 1;170(9):4612-22
references: 12707339
references: Commun Integr Biol. 2010 Sep;3(5):405-8
references: 21057626
references: Nat Immunol. 2007 Mar;8(3):239-45
references: 17304234
references: Curr Opin Immunol. 2007 Jun;19(3):309-14
references: 17433872
references: Nat Cell Biol. 2007 Jun;9(6):654-9
references: 17486113
references: J Immunol. 2004 Dec 15;173(12):7308-16
references: 15585854
references: Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
references: 18228490
references: BMC Genomics. 2007 Mar 06;8:65
references: 17341312
references: Crit Rev Oncol Hematol. 2011 Sep;79(3):213-23
references: 20884225
references: Am J Cancer Res. 2011;1(1):98-110
references: 21969178
references: J Exp Med. 2006 Apr 17;203(4):883-95
references: 16606670
references: Nat Rev Immunol. 2008 Sep;8(9):726-36
references: 19172693
references: Glycoconj J. 2004;19(7-9):565-73
references: 14758081
references: J Immunol. 2009 Jul 15;183(2):993-1004
references: 19561093
references: Stem Cells Dev. 2005 Apr;14(2):204-12
references: 15910247
references: Nature. 2007 Nov 15;450(7168):435-9
references: 17960135
references: J Exp Med. 2000 Oct 2;192(7):1027-34
references: 11015443
references: J Immunol. 2010 May 15;184(10):5885-94
references: 20382885
references: Nat Rev Immunol. 2009 Aug;9(8):581-93
references: 19498381
references: Nature. 2003 Apr 17;422(6933):688-94
references: 12700753
references: Curr Opin Cell Biol. 2009 Aug;21(4):575-81
references: 19442504
references: Immunity. 2001 Jun;14(6):715-25
references: 11420042
references: Nat Cell Biol. 2001 Aug;3(8):708-14
references: 11483955