phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via msc-derived exosomes

Authors

aram mokarizadeh

nowruz delirezh

ahhmad morshedi

ghasem mosayebi

bahram dalir-naghadeh

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.

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Journal title:
veterinary research forum

Publisher: faculty of veterinary medicine, urmia university

ISSN 2008-8140

volume 3

issue 4 2012

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