Th2-high/low哮喘气道上皮细胞差异表达microRNA在哮喘气道炎症中的作用和机制

支气管哮喘可以分为Th2 high和Th2 low两种分子表型，Th2 high哮喘患者气道嗜酸性粒细胞炎症更加严重。气道上皮细胞异常表达的基因参与哮喘气道炎症，我们发现气道上皮细胞IL-25在Th2 high哮喘患者表达异常升高，且与气道嗜酸性粒细胞炎症的程度有显著相关性。microRNA（miRNA）对基因表达进行转录后调节，我们推测Th2 high和low哮喘之间气道上皮细胞差异表达的miRNA及其靶基因在气道嗜酸性粒细胞炎症中有重要作用。在前期工作中，通过对Th2 high和low哮喘患者气道刷片标本进行miRNA芯片检测，发现在Th2 high / low之间存在差异表达miRNA，其中miR-181b-5p的表达水平与气道嗜酸性粒细胞炎症程度有明显的相关性。我们拟研究Th2 high和low哮喘气道上皮细胞差异表达miRNA及其靶基因在气道炎症中的作用，为哮喘治疗提供新的靶点。

Asthma can be classified into different molecular phenotypes such as Th2-high and -low asthma. Eosinophilic inflammation is more severe in Th2-high asthma as compared with Th2-low asthma. Airway epithelial cells play important roles in airway inflammation. We previously found that epithelial IL-25 expression is increased in Th2-high asthma when compared with Th2-low asthma, and is significantly correlated with airway eosinophilic inflammation in asthma. MicroRNAs (miRNAs) regulate gene expression at post-transcription level. We hypothesize that differentially expressed epithelial miRNAs between Th2-high and -low asthma play important roles in airway eosinophilic inflammation in asthma. Our preliminary data identified a set of differentially expressed miRNAs between Th2-high and Th2-low asthma, including miR-181b-5p. Epithelial miR-181b-5p levels were significantly correlated with airway eosinophilic inflammation. We aim to investigate the role of differentially expressed miRNA between Th2-high and -low asthma and their target genes in the pathogenesis of airway eosinophilic inflammation in asthma. This study will identify novel target for asthma therapy.