IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination

• IFNγ-stimulated DC exosomes increase brain myelin and oxidative tolerance.
• IFNγ-stimulated DC exosomes improve remyelination after acute demyelination.
• Nasal administration of IFNγ-stimulated DC exosomes increase myelination in vivo.
• IFNγ-stimulated DC exosomes preferentially target oligodendrocytes.
• IFNγ-stimulated DC exosomes deliver miRNAs involved in differentiation/inflammation.

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.