Th17可能通过IL-17/IL7R调控Jagged1-Notch信号通路影响分泌性中耳炎发生发展的机制

分泌性中耳炎(Secretory Otitis Media，SOM)是以中耳积液及听力下降为主要特征的中耳化脓性炎性疾病，Th17细胞具有重要免疫调节作用，参与分泌性中耳炎免疫调节。本课题组前期研究结果显示IL-17在分泌性中耳炎和肿瘤免疫中起到重要的作用，结合国内外研究进展和课题组前期研究基础，提出如下研究假设：中耳黏膜受损诱导CD4+ T细胞向Th17细胞分化,活化的Th17分泌大量IL-17参与炎症反应,通过IL-17/IL-17R刺激中耳黏膜上皮细胞，激活Jagged1-Notch信号通路调控SOM发生发展。因此本研究以SOM患者外周血,中耳积液标本,构建SOM 小鼠模型,运用CRISPR-Cas9技术,ATAC-seq测序,RNA-seq分析等技术进行研究。阐明Th17细胞可能通过IL-17/IL7R调控Jagged1-Notch信号通路影响SOM生发展的机制。

Secretory otitis media (SOM) is a suppurative inflammatory disease of the middle ear characterized by middle ear effusion and hearing loss. Th17 cells have an important immunoregulatory role and participate in the immune regulation of secretory otitis media. The preliminary research results of this research group show that IL-17 plays an important role in secretory otitis media and tumor immunity. Combining the research progress at home and abroad and the research basis of the research group, the following research hypothesis is proposed: CD4 + T cells are induced by damage to the middle ear Differentiation into Th17 cells, activated Th17 secretes a large amount of IL-17 to participate in the inflammatory response, stimulates the middle ear mucosal epithelial cells through IL-17 / IL-17R, activates the Jagged1-Notch signaling pathway to regulate the development of SOM. Therefore, in this study, SOM patients' peripheral blood and middle ear effusion samples were used to construct a SOM mouse model, using CRISPR-Cas9 technology, ATAC-seq sequencing, RNA-seq analysis and other technologies for research. To clarify the mechanism by which Th17 cells may regulate the Jagged1-Notch signaling pathway through IL-17 / IL7R to affect the growth and development of SOM.