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

骨髓间充质干细胞来源的外泌体包裹的 miR-181a 通过 SIRT1/乙酰化介导的 FOXP3 稳定化诱导 CD4+CD25+FOXP3+ 调节性 T 细胞

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作者:Renyong Wang, Ruixue Li, Tiehan Li, Lei Zhu, Zongze Qi, Xiaokui Yang, Huan Wang, Baoquan Cao, Hong Zhu

Abstract

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.

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