miR-155 contributes to Df1-induced asthma by increasing the proliferative response of Th cells via CTLA-4 downregulation
miR-155 contributes to Df1-induced asthma by increasing the proliferative response of Th cells via CTLA-4 downregulation
复制标题
miR-155 通过下调 CTLA-4 增加 Th 细胞的增殖反应，从而促进 Df1 诱导的哮喘
DOI：
10.1016/j.cellimm.2017.01.005
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发表时间：
2017-04-01
影响因子：
4.3
通讯作者：
Lv, Kun
中科院分区：
文献类型：
--
作者：
Zhang, Yingying;Sun, Entao;Lv, Kun
变应原诱导的气道炎症以肺部Th2介导的嗜酸性粒细胞炎症为特征。然而，导致这种异常Th2反应的分子机制仍不清楚。近期研究表明，微小RNA（miRNAs）可调节过敏性气道炎症。在本研究中，对miRNAs在过敏性哮喘发病机制中的作用进行了检测。通过miRNA微阵列鉴定出差异表达的miRNAs，其中miR - 155在哮喘小鼠肺部表达量最高。对miR - 155过表达的检测结果显示，与对照动物相比，变应原激发的小鼠肺部炎症增强且黏液分泌过多。此外，细胞毒性T淋巴细胞相关抗原4（CTLA - 4）作为T细胞活化的重要负调节因子，被确定为miR - 155的直接靶标。而且，miR - 155在CD4(+) T细胞中过表达导致CTLA - 4水平降低，进而增殖反应增强。综上所述，这些发现表明miR - 155可能通过下调CTLA - 4增加Th细胞的增殖反应，从而促进过敏性哮喘的发生，因此它可能是过敏性哮喘的一个潜在治疗靶点。（C）2017爱思唯尔公司。保留所有权利。
Allergen-induced airway inflammation is characterized by Th2-mediated eosinophilic inflammation in the lungs. While the molecular mechanisms leading to this abnormal Th2 response remain unclear. Recent studies have demonstrated that MicroRNAs (miRNAs) modulate allergic airway inflammation. In this study, the role of miRNAs in allergic asthma pathogenesis was examined. Differentially expressed miRNAs were identified via miRNA microarray, with miR-155 being among the most highly expressed in asthma mice lungs. Examination of miR-155 overexpression resulted in enhanced inflammation and mucus hypersecretion in the lungs of allergen-challenged mice compared with control animals. Furthermore, CTLA-4, an important negative regulator of T-cell activation, was identified as a direct miR-155 target. Moreover, miR-155 overexpression in CD4(+) T cells resulted in decreased CTLA-4 levels and a subsequent increased proliferative response. Collectively, these findings suggest that miR-155 might contribute to allergic asthma by increasing the proliferative response of Th cells via CTLA-4 down regulation and thus may be a potential therapeutic target for allergic asthma. (C) 2017 Elsevier Inc. All rights reserved.