Bone Mesenchymal Stem Cell-Derived Exosome-Enclosed miR-181a Induces CD4(+)CD25(+)FOXP3(+) Regulatory T Cells via SIRT1/Acetylation-Mediated FOXP3 Stabilization

Bone marrow mesenchymal stem cells (BMSCs) have been identified as a potential therapeutic approach to immune-related diseases. Here, we show that BMSC-derived exosomes promote FOXP3 expression and induce the conversion of CD4(+) T cells into CD4(+)CD25(+)FOXP3(+) Treg cells, which is significant for immunosuppressive activity. We found that miR-181a-5p is upregulated in BMSC-derived exosomes and can be transferred to CD4(+) T cells. In CD4(+) cells, miR-181a directly targets SIRT1 and suppresses its expression. Moreover, downregulated SIRT1 enhances FOXP3 via protein acetylation. In conclusion, our data demonstrated that BMSC-derived exosomal miR-181a is critical in the maintenance of immune tolerance. Furthermore, our results reveal that BMSC-derived exosomal miR-181a induces the production of CD4(+)CD25(+)FOXP3(+) Treg cells via SIRT1/acetylation/FOXP3.