title: IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination.
abstract: Dendritic cells (DCs) release exosomes with different characteristics based on stimulus. Here, we showed that DC cultures stimulated with low-level IFNγ released exosomes (IFNγ-DC-Exos) that contained microRNA species that can increase baseline myelination, reduce oxidative stress, and improve remyelination following acute lysolecithin-induced demyelination. Furthermore, nasally administered IFNγ-DC-Exos increased CNS myelination in vivo. IFNγ-DC-Exos were preferentially taken up by oligodendrocytes, suggesting that they directly impact oligodendrocytes to increase myelination. Thus, our results show great potential for use of these IFNγ-DC-Exos as a therapeutic to promote remyelination in multiple sclerosis and dysmyelinating syndromes.
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Aya D
authors.initials: AD
authors.lastname: Pusic
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Kae M
authors.initials: KM
authors.lastname: Pusic
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Benjamin L L
authors.initials: BL
authors.lastname: Clayton
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: rkraig@neurology.bsd.uchicago.edu.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Kraig
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy*; D003713:Dendritic Cells / Q000187:drug effects* / Q000648:ultrastructure; D055354:Exosomes / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000648:ultrastructure; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects
chemical_list: D016898:Interferon-alpha; D008244:Lysophosphatidylcholines; D035683:MicroRNAs; D005978:Glutathione
keywords: Demyelination; Dendritic cell; Exosomes; MicroRNA; Multiple sclerosis; Myelin