Adipose Derived Mesenchymal Stem Cell Exosomes Loaded With Mir-10A Promote the Differentiation of Th17 and Treg From Naive Cd4+ T Cell Publisher Pubmed



Bolandi Z^{1, 2} ; Mokhberian N² ; Eftekhary M² ; Sharifi K^{1, 2} ; Soudi S³ ; Ghanbarian H^{2, 5, 6} ; Hashemi SM^{4, 5, 6} Show Affiliations
Source: Life Sciences Published:2020

Abstract

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, RORγt, and Foxp3 and the secreted levels of IFN-γ, IL-4, IL-17, and TGF-β 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 RORγt and Foxp3 were enhanced and that of T-bet was reduced. Similarly, the secreted levels of IL-17, and TGF-β were increased and that of IFN-γ 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. © 2020