特异性免疫治疗（ASIT）是过敏性哮喘的唯一对因疗法，临床显示尘螨ASIT使感染诱发哮喘加重的发生率下降，与固有免疫增强有关。我们前期研究发现尘螨疫苗含肠杆菌菌毛（Fim）H蛋白（JACI，2014），可上调小鼠肺上皮细胞β防御素-3（人β防御素[HBD] -2同系物）表达，增加肺部感染的抵抗力，其机制未明，故提出“尘螨疫苗双功能假说”。本研究对尘螨过敏哮喘患者进行ASIT，分析治疗前后诱导痰、鼻腔灌洗液HBD-2蛋白、树突状细胞（DC）分泌因子水平、DC亚型和Th1/Th2细胞比例及肺上皮细胞HBD-2 mRNA水平，观察上述指标与症状、用药及肺功能变化的关系；通过体外细胞实验、小鼠哮喘动物模型及Toll样受体（TLR）4基因敲除鼠，研究尘螨疫苗诱导HBD-2表达信号通路、调节气道黏膜DC亚型转换方式以及诱导DC成熟并调控Th分化的方向，揭示ASIT对呼吸道固有免疫的调节机制。

Allergen specific immunotherapy (ASIT) is the only treatment that can modify the natural course of allergic asthma. Clinical investigation has shown a significant reduction in occurrence of asthma exacerbation induced by pulmonary infection in patients with ASIT with dust mite vaccince . This might be associated with the enhancement of innate immunity function. We have found Fim H protein of enterobacter in dust mite vaccine, which can protect from lower airway infection by up-regulating the expression of mouse beta-definsin-3 (homolog for human beta-defensin [HBD]-2) of airway epithelium in mouse model. However, the detail mechanism has not been clarified. We propose the hypothesis of two-way regulations of house dust mite vaccination. This project is designed to analyze the levels of HBD-2 in induced sputum, nasal lavage, and secretory mediators by the dendrictic cells (DC), DC subtype, ratio of T helper cell (Th) 1 and Th2 in alveolar lavage, and level of HBD-2 mRNA in airway epithelium in allergic patients before and after ASIT. Associations between clinical improvements including symptom and medication scores and pulmonary functions and the above pulmonary immunological biomarkers are evaluated. The project also applies for in vitro cellular experiments, asthmatic mouse model and Toll like receptor (TLR) 4 knockout mice to investigate signal pathway of HBD-2 expression, regulation of pattern of DC subtype exchange in airway mucosa, and pivotal factors in inducing DC maturation and modulating Th polarization. We would be able to reveal the regulatory mechanisms of respiratory innate immunity with ASIT in this project.