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

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.

Exosome-derived microRNAs: emerging players in vitiligo

“…In addition, bone marrow-derived mesenchymal stem cell (BMSC)-derived exosome miR-181a is essential for the maintenance of immune tolerance. It induced CD3+CD1+FOXP3+ Treg cells production via SIRT4/acetylation/FOXP3 ( 158 ). BMSC-derived exosomes can partially transfer miR-17a-6p to suppress IL-23 expression and thereby balance the Th17/Treg ratio in aplastic anemia ( 159 ).…”

Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma

“…It has been reported that miRNA-181 is overexpressed in CD138 + PCs from MM patients [ 9 , 77 ]. miR-181 is released to BME by BMSC-derived exosomes and may be uptaken by PCs [ 78 ]. This miRNA epigenetically regulates the tumor-suppressor activity of p53 and Sirtuin 1 (SIRT1) [ 9 , 78 ].…”

“…miR-181 is released to BME by BMSC-derived exosomes and may be uptaken by PCs [ 78 ]. This miRNA epigenetically regulates the tumor-suppressor activity of p53 and Sirtuin 1 (SIRT1) [ 9 , 78 ]. Sirt1 is a histone deacetylase (HDAC) and plays an important role in epigenomic profiling in MM by modulating the expression of P53 and miRNA-34a, and its targeting is suggested as a treatment strategy for MM [ 31 ].…”