miR-22 controls Irf8 mRNA abundance and murine dendritic cell development.

miR-22 controls Irf8 mRNA abundance and murine dendritic cell development.
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DOI:
10.1371/journal.pone.0052341
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Watowich SS
Watowich SS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li HS;Greeley N;Sugimoto N;Liu YJ;Watowich SS

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MicroRNA (miRNA) 通过 miRNA 诱导的沉默复合物 (miRISC) 或 miRNA 核糖核蛋白复合物 (miRNP) 介导的基因抑制作用,已成为许多细胞反应的关键调节因子。在这里,我们研究了 miRNA 在树突状细胞 (DC) 发育中的作用,树突状细胞是一种重要的免疫细胞类型,分为传统 DC (cDC) 和浆细胞样 DC (pDC) 亚群。我们发现,与 pDC 相比,miR-22 在小鼠 CD11c+ CD11b+ B220− cDC 中高表达,并且在 DC 祖细胞培养物中用 GM-CSF 诱导,刺激 CD11c+ CD11b+ B220− cDC 分化。在 DC 发育过程中强制过度表达 miR-22 可增强 CD11c+ CD11b+ B220− cDC 的生成,但会损害 pDC,而 miR-22 敲除则表现出相反的效果。此外,miR-22的过表达和敲低对Irf8的mRNA丰度显示出显着影响,Irf8编码在DC发育中发挥重要作用的转录因子IRF8。荧光素酶报告基因检测证实 miR-22 直接结合小鼠 Irf8 mRNA 的 3'UTR。总的来说,这些结果表明 miR-22 靶向 Irf8 mRNA 进行转录后抑制并控制 DC 亚群分化。
MicroRNAs (miRNAs) have emerged as critical regulators of many cellular responses, through the action of miRNA-induced silencing complex (miRISC)- or miRNA ribonucleoprotein complex (miRNP)-mediated gene repression. Here we studied the role of miRNAs in the development of dendritic cells (DCs), an important immune cell type that is divided into conventional DC (cDC) and plasmacytoid DC (pDC) subsets. We found that miR-22 was highly expressed in mouse CD11c+ CD11b+ B220− cDCs compared to pDCs, and was induced in DC progenitor cell cultures with GM-CSF, which stimulate CD11c+ CD11b+ B220− cDC differentiation. Enforced overexpression of miR-22 during DC development enhanced CD11c+ CD11b+ B220− cDC generation at the expense of pDCs, while miR-22 knockdown demonstrated opposite effects. Moreover, overexpression and knockdown of miR-22 showed significant effects on the mRNA abundance of Irf8, which encodes the transcription factor IRF8 that plays essential roles in DC development. Luciferase reporter assays confirmed that miR-22 binds directly to the 3′UTR of the mouse Irf8 mRNA. Collectively, these results suggest that miR-22 targets Irf8 mRNA for posttranscriptional repression and controls DC subset differentiation.
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