Zhang Yingying, Sun Entao, Li Xueqin, Zhang Mengying, Tang Zongsheng, He Ling, Lv Kun
Laboratory Medicine of Yijishan Hospital, Wannan Medical College, Wuhu 241001, PR China.
Department of Medical Parasitology, Wannan Medical College, Wuhu 241002, PR China.
Cell Immunol. 2017 Apr;314:1-9. doi: 10.1016/j.cellimm.2017.01.005. Epub 2017 Jan 7.
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 downregulation and thus may be a potential therapeutic target for allergic asthma.
变应原诱导的气道炎症的特征是肺部由Th2介导的嗜酸性粒细胞炎症。然而，导致这种异常Th2反应的分子机制仍不清楚。最近的研究表明，微小RNA（miRNA）可调节变应性气道炎症。在本研究中，研究了miRNA在变应性哮喘发病机制中的作用。通过miRNA微阵列鉴定出差异表达的miRNA，其中miR-155是哮喘小鼠肺中表达最高的miRNA之一。与对照动物相比，对miR-155过表达的检测结果显示，变应原激发的小鼠肺中炎症增强且黏液分泌过多。此外，CTLA-4是T细胞活化的重要负调节因子，被确定为miR-155的直接靶标。此外，CD4 T细胞中miR-155过表达导致CTLA-4水平降低，随后增殖反应增加。总的来说，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，从而导致变应性哮喘，因此可能是变应性哮喘的一个潜在治疗靶点。
