重症哮喘具有很高的住院率及病死率，近年来发现IL-23/Th17炎症轴在重症哮喘的发病中扮演重要角色，但具体机制尚未清楚。前期我们发现粉尘螨非过敏原蛋白Cystatin-L能诱发小鼠嗜中性粒细胞型重症哮喘，且小鼠血清中IL-23、IL-17和中性粒细胞显著升高，进一步研究发现尘螨非过敏原蛋白Cystatin-L通过调节树突状细胞（DC细胞）功能间接促进Th17的分化，但对DC细胞功能具体调节机制还不清楚。本研究提出尘螨非过敏原蛋白Cystatin-L通过调节DC细胞功能从而激活IL-23/Th17炎症轴诱发重症哮喘的假说。本课题将通过动物及细胞实验，探讨尘螨非过敏原蛋白Cystatin-L通过调节DC细胞功能激活IL-23/Th17（IL-17）炎症轴诱发重症哮喘的作用机制；并分析尘螨Cystatin-L蛋白与临床不同类型重症哮喘的相关性。研究结果将为不同类型重症哮喘防治提供新的理论依据。

In recent years, it has been found that IL-23 / Th17 inflammatory axis plays an important role in the pathogenesis of severe asthma, but the specific mechanism is not clear. In the early stage, we found that dust mite non allergen protein cystatin-l can induce mouse neutrophil type of severe asthma, and the level of IL-23, IL-17 and neutrophils in mouse serum increased significantly. Further research found that dust mite non allergen protein cystatin-l indirectly promoted Th17 differentiation by regulating the function of dendritic cells (DC cells), but the specific regulatory mechanism of DC cell function is unclear Chu. In this study, we hypothesized that cyclostatin-l, a non allergen protein of dust mite, can activate IL-23 / Th17 inflammatory axis to induce severe asthma by regulating DC cell function. In this study, we will investigate the mechanism of dust mite non allergen protein cystatin-l activating IL-23 / Th17 (IL-17) inflammatory axis by regulating DC cell function to induce severe asthma through animal and cell experiments, and analyze the correlation between dust mite cystatin-l protein and clinical different types of severe asthma. The results will provide a new theoretical basis for the prevention and treatment of different types of severe asthma.