MiR-155 contributes to Th17 cells differentiation in dextran sulfate sodium (DSS)-induced colitis mice via Jarid2
MiR-155 contributes to Th17 cells differentiation in dextran sulfate sodium (DSS)-induced colitis mice via Jarid2
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MiR-155 通过 Jarid2 促进葡聚糖硫酸钠 (DSS) 诱导的结肠炎小鼠的 Th17 细胞分化
DOI：
10.1016/j.bbrc.2017.04.143
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发表时间：
2017
影响因子：
3.1
通讯作者：
Yujin Liu
中科院分区：
文献类型：
--
作者：
Meng Xu;Dongmei Zuo;Xingxing Liu;Heng Fan;Qianyun Chen;Shuangjiao Deng;Zhexing Shou;Qing Tang;Jia Yang;Zhen Nan;Hui Wu;Yalan Dong;Yujin Liu
microRNA（miRNAs）通过mRNA的不稳定或抑制翻译在调节免疫系统功能中发挥重要作用。最近，检测到miR-155在活动性UC患者的结肠组织中显著上调。然而，miR-155是否参与UC的发病机制以及其如何影响葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠中的免疫应答尚不清楚。在这里，我们研究了miR-155在UC中的作用。首先，通过生物信息学分析和荧光素酶报告试验，发现Jarid 2是miR-155的直接靶点;然后，我们通过原位杂交、免疫荧光和流式细胞术，发现DSS诱导的小鼠中miR-155水平升高，Jarid 2水平降低，Th 17细胞频率升高;我们还使用慢病毒载体来递送miR-155抑制序列以沉默被上皮细胞有效摄取的miR-155。MiR-155抑制减轻DSS诱导的结肠损伤，并抑制Th 17细胞分化。这项研究表明，miR-155在DSS诱导的结肠炎小鼠中发挥宿主损伤作用，并通过靶向Jarid 2诱导Th 17分化。
MicroRNAs (miRNAs) play an important role in regulating immune system function by mRNA destabilisation or inhibition of translation. Recently, miR-155 was detected to be significantly up-regulated in.colonic tissues of patients with active UC. However, it is unknown whether miR-155 is involved in the.pathogenesis of UC and how it influences immune response in dextran sulfate sodium (DSS)-induced.colitis mice. Here, we investigated the role of miR-155 in UC. Firstly, through bioinformatics analysis and.luciferase report assay, we found Jarid2 was a direct target of miR-155; then, we carried out in situ.hybridization, immunofluorescence and flow cytometry, and revealed that miR-155 levels were.increased, Jarid2 levels were decreased and the frequency of Th17 cells was elevated in DSS-induced.mice; we also used lentiviral vector to deliver miR-155 inhibition sequences to silence miR-155 that.was effectively taken up by epithelial cells. MiR-155 inhibition attenuated DSS-induced colonic damage.and inhibited Th17 cells differentiation. This study suggests that miR-155 plays a host-damaging role.during DSS-induced colitis mice and induces Th17 differentiation by targeting Jarid2.