MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1.

MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1.
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MicroRNA-155 通过靶向 SOCS1 调节 Treg 和 Th17 细胞分化以及 Th17 细胞功能

DOI:
10.1371/journal.pone.0046082
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Liao YH
Liao YH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yao R;Ma YL;Liang W;Li HH;Ma ZJ;Yu X;Liao YH

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MicroRNA(MiR)-155在先天性免疫反应和获得性免疫反应中都发挥着重要作用。它可以影响CD4+T细胞谱系的选择。为了阐明miR-155在CD4+CD25+调节性T(Treg)/辅助性T细胞(Th)17细胞分化和功能中的作用及其机制,我们通过将前miR-155和抗miR-155导入纯化的CD4+T细胞进行了功能获得和功能丧失的分析。结果表明,miR-155对Treg和Th17细胞的分化均有正向调节作用。可诱导Th1 7细胞释放IL-17A,但不能诱导Treg细胞释放IL-10和转化生长因子-β1。此外,我们还发现,在Treg和Th17细胞分化过程中,miR155通过调节Janus激酶/信号转导和转录激活子(JAK/STAT)而不是转化生长因子-β/MOMORS来对抗十核瘫痪同源蛋白(SMAD)信号通路。这可能是因为JAK/STAT信号通路的重要负调控因子细胞因子信号传导抑制因子(SOCS)1是miR-155在这一过程中的直接靶点,而Smad2和Smad5不是。因此,我们证明miR-155通过靶向SOCS1促进Treg和Th17细胞的分化和IL-17A的产生。
MicroRNA (miR)-155 is a critical player in both innate and adaptive immune responses. It can influence CD4+ T cell lineage choice. To clarify the role of miR-155 in CD4+ CD25+ regulatory T (Treg)/T helper (Th)17 cell differentiation and function, as well as the mechanism involved, we performed gain-and loss-of-function analysis by transfection pre-miR-155 and anti-miR-155 into purified CD4+ T cells. The results showed that miR-155 positively regulated both Treg and Th17 cell differentiation. It also induced the release of interleukin (IL)-17A by Th17 cells, but not the release of IL-10 and transforming growth factor (TGF)-β1 by Treg cells. Furthermore, we found that miR-155 reacted through regulating Janus kinase/signal transducer and activator of transcription (JAK/STAT) rather than TGF-β/mothers against decapentaplegic homolog (SMAD) signaling pathway in the process of Treg and Th17 cells differentiation. This may because suppressors of cytokine signaling (SOCS)1, the important negative regulator of JAK/STAT signaling pathway, was the direct target of miR-155 in this process, but SMAD2 and SMAD5 were not. Therefore, we demonstrated that miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by targeting SOCS1.
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