特应性皮炎（AD）是常见的过敏性皮肤病并常于成年期伴发哮喘，这种过敏性疾病进程被称为过敏进程。研究表明表皮受抗原刺激后产生的胸腺基质淋巴生成素（TSLP）是启动过敏进程的关键分子。本项目前期研究通过构建动物模型发现TSLP可通过活化2型固有淋巴样细胞（ILC2）参与过敏进程小鼠皮肤和气道的免疫反应，同时发现小鼠皮肤和气道中嗜碱性粒细胞数量显著升高。采用嗜碱性粒细胞缺陷小鼠和TSLPR敲除小鼠进行预实验发现敲除嗜碱性粒细胞或敲除TSLP均可减轻过敏进程小鼠的皮肤和气道炎症，提示TSLP可能通过活化嗜碱性粒细胞参与过敏进程的免疫炎症反应。因此本项目拟在前期研究基础上，进一步阐明嗜碱性粒细胞活化在“AD-哮喘”过敏进程中的作用，并明确嗜碱性粒细胞是否依赖于TSLP通路活化、并与ILC2协同作用参与过敏进程小鼠皮肤和气道的炎症反应。对这一机制的阐明将有助于预防哮喘的发病及整体防控过敏性疾病进程。

Atopic dermatitis (AD) is a common allergic skin disease, which is associated with an increased risk of developing asthma and allergic rhinitis later in life. The progression from AD to other allergic diseases was described as ‘atopic march’. It has been demonstrated that the defective skin barrier function and environmental antigen sensitization via skin in early life is the important pathological linkage between AD and asthma. It has been proved that thymic stromal lymphopoietin (TSLP), which is mainly produced by epithelial cells and keratinocytes after stimulation by antigen, is a key molecule in the initiation of atopic march. In our previous study based on atopic march mice models, we found that TSLP can activate type 2 innate lymphoid cells (ILC2) in the skin and airway inflammation and the number of basophils in skin and airway of the mice is significantly increased. Preliminary experiments with basophils deficient mice and TSLPR knockout mice revealed that inhibition of basophils or TSLP can alleviate skin and airway inflammation in atopic march mice, suggesting that basophils might play an important role in atopic march. Therefore, this project aims to elucidate the role of basophils activation in the "AD-asthma" atopic march, and to clarify the molecular mechanism of TSLP elicited basophils responses in skin and lung inflammation. Elucidation of this mechanism will contribute to provide a theoretical basis for the prevention of the onset of asthma and the progression of atopic march.