间充质干细胞外泌体 miR-1470 通过诱导 P27KIP1 的表达促进哮喘患者 CD4^+CD25^+FOXP3^+Treg 的分化。
MSCs exosomal miR-1470 promotes the differentiation of CD4CD25FOXP3 Tregs in asthmatic patients by inducing the expression of P27KIP1.
机构信息
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Department of Respirology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
出版信息
Int Immunopharmacol. 2019 Dec;77:105981. doi: 10.1016/j.intimp.2019.105981. Epub 2019 Nov 2.
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 CD4CD25FOXP3 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 CD4CD25FOXP3 Tregs in CD4 T cells. P27KIP1 knockdown via siRNA silencing significantly inhibited the proportion of CD4CD25FOXP3 Tregs with over-expression of miR-1470, which indicates that miR-1470 induces the differentiation of CD4CD25FOXP3 Tregs through P27KIP1.
间充质干细胞（MSCs）来源的外泌体具有与 MSCs 相似的免疫调节作用。有研究表明，与成纤维细胞来源的外泌体相比，MSCs 外泌体中含有更高水平的 miR-1470。在这里，我们发现 MSCs 来源的外泌体 miR-1470 可以增加哮喘患者中 CD4CD25FOXP3 调节性 T 细胞（Tregs）的比例。此外，机制研究表明，miR-1470 可以通过直接靶向 c-Jun mRNA 的 3' 区域促进 P27KIP1 的上调。此外，miR-1470 模拟物转染可以显著上调 CD4 T 细胞中 CD4CD25FOXP3 Tregs 的比例。通过 siRNA 沉默敲低 P27KIP1 可显著抑制 miR-1470 过表达时 CD4CD25FOXP3 Tregs 的比例，这表明 miR-1470 通过 P27KIP1 诱导 CD4CD25FOXP3 Tregs 的分化。
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