Adipose derived mesenchymal stem cell exosomes loaded with miR-10a promote the differentiation of Th17 and Treg from naive CD4⁺ T cell

Aims: The balance between various CD4(+) T cell subsets through highly regulated differentiation of naive T cells is critical to ensure proper immune response, disruption of which may cause autoimmunity and cancers. miR-10a has been reported to regulate the fate of naive T cells. Mesenchymal stem cells (MSC) derived exosomes are known effective immunomodulators and ideal vehicles for delivery of microRNAs. This study was aimed to examine the impacts of miR-10a on CD4(+) cell fate upon exosomal delivery in combination with immunomodulatory effects of MSCs. Main methods: Exosomes isolated form adipose tissue derived mesenchymal stem cells (AD-MSC-Exo) were transfected with miR-10a and added to naive T cells purified from mouse spleen. AD-MSC-Exos were characterized and the efficacy of miR-10a delivery was evaluated. The expression levels of T-bet, GATA3, ROR gamma t, and Foxp3 and the secreted levels of IFN-gamma, IL-4, IL-17, and TGF-beta respectively specific to Th1, Th2, Th17 and Treg, were assessed by qPCR and ELISA. Key findings: Being transferred by AD-MSC-Exo, miR-10a was effectively induced in CD4(+) T cells. Upon treatment with miR-10a loaded exosomes, the expression levels of ROR gamma t and Foxp3 were enhanced and that of T-bet was reduced. Similarly, the secreted levels of IL-17, and TGF-beta were increased and that of IFN-gamma was decreased. Significance: Our data indicate that miR-10a loaded exosomes, promote Th17 and Tregs response while reduce that of Th1. Promotion of both Th17 and Tregs in concert, mediated by the combined effect of miR-10a and MSC-Exo, indicate new therapeutic potentials, particularly in line with novel anti-tumor immunotherapeutic strategies.