Aram Mokarizadeh - Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Nowruz Delirezh - Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Ahhmad Morshedi - Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Ghasem Mosayebi - Department of Immunology and Microbiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
Bahram Dalir-Naghadeh - Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

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 MOG۳۵-۵۵ peptide. After ۲۴ hr, insertion of exosomal tolerogenic molecules (PD-L۱, TGF-β, galectin-۱) 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-۱۷. 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-۱۷ 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.

Auto-reactive cell, EAE, MSC, Exosome, Tolerogenic molecule