MSCs exosomal miR-1470 promotes the differentiation of CD4+CD25+FOXP3+ Tregs in asthmatic patients by inducing the expression of P27KIP1

Abstract

Exosomes derived from Mesenchymal Stem Cells (MSCs) possesses similar immunomodulatory effect as MSCs. It had been suggested that MSCs exosomes contain higher level of miR-1470 compared to exosomes derived from fibroblast. Here, we show that MSCs exosomal miR-1470 can elevate the proportion of CD4⁺CD25⁺FOXP3⁺ regulatory T cells (Tregs) in asthmatic patients. Moreover, mechanistic studies revealed that miR-1470 can promote the upregulation of P27KIP1 by directly targeting the 3' region of c-Jun mRNA. Furthermore, miR-1470 mimic transfection could significantly upregulate the proportion of CD4⁺CD25⁺FOXP3⁺ Tregs in CD4⁺ T cells. P27KIP1 knockdown via siRNA silencing significantly inhibited the proportion of CD4⁺CD25⁺FOXP3⁺ Tregs with over-expression of miR-1470, which indicates that miR-1470 induces the differentiation of CD4⁺CD25⁺FOXP3⁺ Tregs through P27KIP1.