miR-155-5p/TLE4轴通过激活Wnt/β-catenin信号通路活化ILC2s诱发变应性鼻炎的机制研究

2型固有淋巴细胞（ILC2s）参与了变应性鼻炎（AR）的发生发展，但其调节机制尚不清楚。课题组前期研究发现ETS1、miR-155-5p和ILC2s均在AR中高表达并呈正相关；TLE4在激活的ILC2s中低表达，且与miR-155-5p存在结合位点；而Wnt/β-catenin信号通路关键分子在AR中高表达，可能介导调控ILC2s诱发AR的功能。所以本课题假设：ETS1通过miR-155-5p下调TLE4，进而激活Wnt/β-catenin信号通路，促进ILC2s介导的炎症反应和AR的发生。为此，本项目拟在检测AR相关各基因（ETS1、miR-155-5p/TLE4）及信号通路表达的基础上，通过siRNA干扰和基因敲除等方法在体外试验和动物试验中验证相关分子机制，从miR调节ILC2s的角度阐明AR的发病机制并为精准治疗提供新的分子靶点。

Group 2 Innate Lymphoid Cells (ILC2s) are reported to be involved in the pathogenesis of allergic rhinitis (AR). However, the molecular regulation of ILC2s has not been fully understood. Our previous studies demonstrated that ILC2s, ETS1 and miR-155-5p expression were significantly increased in AR patients. TLE4, which there is a binding site with miR-155-5p, is decreased in ILC2s. And the key molecules of Wnt/β-catenin signaling pathway are highly expressed in AR. We thus hypothesized that ETS1 down-regulates TLE4 through miR-155-5p, and then activates Wnt/β-catenin signaling pathway, which promotes ILC2s-mediated inflammatory response. We plan to detect the expression of AR-related genes (ETS1, miR-155-5p/TLE4) and signaling pathways, and verify the relevant molecular mechanisms in vitro and animal experiments through siRNA interference and gene knockout methods techniques. To elucidate the mechanism of AR from the perspective of miR-regulating may be beneficial for the establishment of novel precision treatment.