过敏性疾病尚没有普遍有效的治疗方法，其病理机制的研究，进一步寻找对过敏疾病有重要调控作用的基因，寻找新的治疗靶点，采用多靶点联合治疗，有重要的医学及社会经济意义。我们前期工作通过生物信息学推测、高通量筛选及初步免疫学验证，发现一个钙结合蛋白S100A4在过敏中起重要作用，但作用机制不明。本课题拟就小鼠过敏性哮喘模型研究S100A4在过敏病理过程中的作用机制，包括阻断该蛋白表达后过敏性哮喘相关症状的变化，该蛋白在哮喘模型中的产生细胞及对效应细胞的过敏性激活过程及作用通路的调节；并进一步研究过敏性哮喘病人外周血中S100A4水平与免疫细胞及免疫因子的相关性，及与哮喘病人外周血中过敏相关因子的相互作用，并结合病情病程，探索S100A4在过敏性哮喘疾病中作为治疗靶点的可能性。研究结果将为过敏性疾病如过敏性哮喘提供新的诊断及疗效评估、预后提供基础理论依据。

The prevalence of allergic disease has increased significantly during the last few decades and no satisfactory therapies are available up to now. There is an urgent need to identify new treatment targets for allergic diseases. We have recently predicted by bioinformatics and high-throughput screening that the calcium-binding protein S100A4 may play a pivotal role in allergy, which was preliminarily confirmed in a mouse model of dermatitis. But the possible mechanisms and applications have not been investigated. In the present project, we aim to further validate the role of S100A4 in allergy by establishing a mouse asthma model. Detailed analyses will be undertaken to dissect the roles of S100A4 in asthma. In addition to the mouse in vivo model, we will also systematically investigate the effect of S100A4 in the allergic activation of mast cells, a cell type with recognised contribution to allergic inflammation. Further investigation on the correlation of clinical information from patients with allergic asthma and the S100A4 level will be intensively addressed to evaluate the possibility of S100A4 as a therapeutic target in allergic asthma.