Bach2抑制IL-33诱导Th2细胞分化在变应性鼻炎中的机制研究

Allergic rhinitis（AR）is a chronic inflammation of the nasal mucosa disease, with high incidence，seriously affecting patient's health. Studies have shown that IL-33 plays an important role in the pathogenesis, because antagonizing it can effectively relieve AR disease. So, exploring the pathogenic and regulation mechanism of IL-33 is of great significance. Bach2, a transcriptional inhibitory factor, can directly inhibit Th2 cell differentiation and cytokine release, which are related to asthma and other immune diseases. We found that Bach2 expression was significantly decreased during IL-33-induced Th2 differentiation. Overexpression of Bach2 could effectively inhibit the release of IL-33-induced Th2 cytokines, but the molecular mechanism was not clear. In this research, we will establish AR mouse model to explore the molecular mechanism of IL-33-induced Th2 differentiation; to explore the molecular mechanism between Bach2 and IL-33 signal pathway, which can provide new treatment for AR.

变应性鼻炎（AR）发病率高，危害重，严重影响患者身体健康。研究表明IL-33在AR发病中起重要作用；拮抗IL-33能有效缓解AR病情。为此，探讨IL-33在AR中的致病机制及调控机制具有重要意义。Bach2是最新发现的转录抑制因子，能直接抑制Th2型炎症发生，与哮喘等免疫性疾病密切相关。我们前期研究发现，Bach2在IL-33诱导Th2细胞分化过程中表达逐渐降低；过表达Bach2可以有效抑制IL-33诱导的Th2细胞因子释放；但具体分子机制并不清楚。本课题拟在前期研究基础上，采用实验动物模型结合分子细胞学方法，研究IL-33诱导Th2细胞分化的分子机制；研究Bach2负性调控Th2细胞中IL-33信号通路的具体机制，为治疗AR提供新思路。

变应性鼻炎（AR）发病率高，危害重，严重影响患者身体健康。研究表明IL-33诱导的Th2型炎症反应在AR发病中起重要作用；拮抗IL-33能有效缓解AR病情。为此，探讨IL-33诱导Th2细胞分化和/或Th2细胞因子产生的调控机制对于治疗AR具有非常重要意义。Bach2是最新发现的转录抑制因子，能直接抑制Th2型炎症发生，与哮喘等免疫性疾病密切相关。本项目首先构建了Bach2条件敲除小鼠模型，并通过体内外实验证明了缺乏Bach2调控将加重小鼠呼吸道IL-33相关Th2型炎症反应，而在Th2细胞内上调Bach2表达将有效抑制IL-33相关Th2细胞因子的释放；其抑制机制主要是Bach2绑定到Th2型细胞因子基因的CIRE区域和RHS6区域，进而调控Th2型细胞因子基因的表达。