IL-23/IL-17轴在MYB促咽喉上皮内病变过程中的作用及机制研究

咽喉白斑病、角化症等疾病临床定义为咽喉癌前病变，多表现为粘膜上皮增生、过度角化、异型增生等，病理上统称为鳞状上皮内病变（SIL）。目前对于SIL的发生机制仍未完全阐明，临床防治也无统一标准。我们前期研究发现，K5-Myb转基因小鼠在表皮及咽喉粘膜出现类似上述SIL表现，说明MYB有促SIL作用。同时我们GSEA分析发现IL-23/IL-17轴与MYB紧密相关，但其在MYB促SIL过程中的作用及机制尚不十分清楚。本项目拟在此基础上，通过建立MYB过表达HOK细胞模型及K5-Myb咽喉SIL小鼠模型，分别从细胞及动物水平阐明MYB如何调控IL-23/IL-17轴及外源性通路激活IL-23/IL-17轴协同加速MYB促SIL的作用及机制。同时结合临床病例分析，阐明两者与SIL分级及临床预后的相关性。本项目的研究结果将为咽喉白斑病等的治疗提供新思路，并为咽喉癌前病变的早期筛查及预后评估开辟新靶点。

Leukoplakia and keratosis of pharynx and larynx are clinically defined as precancerous lesions of the pharynx and larynx, which are pathologically manifested by mucosal epithelial hyperplasia, hyperkeratosis, dysplasia, collectively defined as squamous intraepithelial lesions (SIL). The mechanisms of SIL have not been fully elucidated, and there is no unified standard for clinical prevention and treatment so far. In our previous study, we found that K5-MYB transgenic mice showed epithelial hyperplasia and keratosis and other SIL manifestations in epidermis and laryngopharyngeal mucosa, indicating that MYB could induce SIL. On the other hand, our GSEA analysis indicated that the IL-23/IL-17 axis was significantly related to MYB, however the role and mechanism of the IL-23/IL-17 axis in MYB induced SIL is unclear. Based on our previous study, this project aims to clarify how MYB regulates the IL-23/IL-17 axis and the role and mechanism of IL-23/IL-17 axis in SIL induced by MYB at the cellular and animal levels respectively by establishing MYB overexpressing HOK cell model and K5-MYB laryngopharyngeal SIL mouse model. Meanwhile, with clinical case analysis, we plan to clarify the correlation of MYB, IL-23/IL-17 axis and SIL grading and clinical prognosis. The results of this project will provide new ideas for the treatment of leukoplakia and keratosis of pharynx and larynx etc., and could also provide guidance for the early screening and prognosis evaluation of pharyngeal precancerous lesions.