MiR-199a-3p modulates the function of dendritic cells involved in transplantation tolerance by targeting CD86.

Abstract

Dendritic cells (DCs) are key components of the immune system, serving as antigen-presenting cells to activate adaptive immunity. Whereas mature DCs promote immune responses, immature DCs induce or maintain immunological tolerance by downregulating T-cell responses. Therefore, DCs are potent antigen (Ag)-presenting cells in the immune system. MicroRNAs are noncoding RNAs that posttranscriptionally regulate mRNA by binding the 3'-untranslated region (UTR) of these molecules, modulating their expression. Many recent studies have suggested a potential role of miRNAs in DCs maturation and differentiation, but the exact mechanisms governing this process are unclear. How and whether miR-199a-3p affects DC maturation has not been investigated. Here, we found that MiR-199a-3p levels are correlated with DC maturation, inflammatory cytokine secretion, and PI3K/AKT/NF-κB signaling pathway activity. In addition, we analyzed the stimulation of regulatory T-cells by DCs. Through this work, we determined CD86 to be targeted by miR-199a-3p, thereby linking it to DC maturation. miR-199a-3p therefore directly inhibits CD86 expression via 3'-UTR targeting, subsequently prolonging allograft survival in a mouse heart transplantation model. miR-199a-3p over-expression may therefore be a potential therapeutic strategy for use in organ transplantation or patients with autoimmune diseases.