miR-340 Alleviates Psoriasis in Mice through Direct Targeting of IL-17A
miR-340 Alleviates Psoriasis in Mice through Direct Targeting of IL-17A
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miR-340 通过直接靶向 IL-17A 减轻小鼠牛皮癣
DOI：
10.4049/jimmunol.1800189
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发表时间：
2018-09-01
影响因子：
4.4
通讯作者：
Ruan, Qingguo
中科院分区：
文献类型：
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作者：
Bian, Jiang;Liu, Ruiling;Ruan, Qingguo
Th17 细胞是众所周知的 CD4+ 效应 Th 细胞谱系，可选择性产生 IL-17A，并在自身免疫性疾病的发病机制中发挥关键作用。 microRNA (miRNA) 是一种小的非编码 RNA 分子，在基因表达的转录后调控中发挥作用。近年来，越来越多的研究表明，多种自身免疫性疾病患者体内多种miRNA失调，并至少部分通过调节Th17反应介导自身免疫性疾病的病理状态。然而，迄今为止发现的少数可能在 Th17 细胞分化中发挥作用的 miRNA 中，它们都通过靶向 Th17 分化的负调节因子或正调节因子来调节 Th17 反应。在当前的研究中，我们试图鉴定能够直接调节IL-17A表达的新miRNA，IL-17A是Th17细胞产生的最重要的细胞因子。我们的结果表明，小鼠IL-17A的3'非翻译区可以作为负调控元件下调基因表达。进一步研究发现miR-340可以特异性结合小鼠IL-17A的3'非翻译区并下调内源性IL-17A的表达。更重要的是，我们证明，miR-340 治疗可通过下调 IL-17A 来减轻小鼠中咪喹莫特诱导的银屑病的临床严重程度。这些数据表明 miR-340 可能是治疗牛皮癣和其他 IL-17A 介导的自身免疫性疾病的有用治疗靶点。
Th17 cell is a well-known lineage of CD4+ effector Th cells that selectively produce IL-17A and play critical roles during the pathogenesis of autoimmune disease. A microRNA (miRNA) is a small noncoding RNA molecule that functions in posttranscriptional regulation of gene expression. Recently, an increasing number of studies have demonstrated that multiple miRNAs are dysregulated in patients with various autoimmune diseases and mediate autoimmune disease pathologic condition at least in part through the regulation of Th17 response. However, among the few miRNAs identified so far that play possible roles in the differentiation of Th17 cells, they all regulate the Th17 response through targeting negative or positive regulators of Th17 differentiation. In the current study, we sought to identify new miRNAs that can directly regulate the expression of IL-17A, the most important cytokine produced by Th17 cells. Our results showed that the 3′ untranslated region of mouse IL-17A can act as a negative regulatory element to downregulate gene expression. Further study revealed that miR-340 can specifically bind to the 3′ untranslated region of mouse IL-17A and downregulate the expression of endogenous IL-17A. More importantly, we demonstrated that treatment with miR-340 alleviates the clinical severity of imiquimod-induced psoriasis in mice through the downregulation of IL-17A. These data indicate that miR-340 may be a useful therapeutic target for the treatment of psoriasis and other IL-17A–mediated autoimmune diseases.