激素不敏感的重症哮喘是哮喘致死的主因。气道浸润中性粒细胞介导气道损伤是重症哮喘的主要病理特征。近来pDC在哮喘中的作用逐渐被认识，但是否与调控中性粒细胞炎症有关，尚不明晰。本项目预初实验发现，在HDM或Papain诱导的哮喘模型的致敏期或激发期敲除pDC均增强气道中性粒细胞浸润，且哮喘小鼠肺组织pDC聚集并高表达TGF-β1。在哮喘小鼠的激发期体内给予pDC可纠正Treg/Th17平衡紊乱。进一步发现，TGF-β1可以抑制HDM诱导的上皮细胞表达CXCL1。遂提出如下假设：致敏原诱导pDC分泌TGF-β1不仅纠正Treg/Th17平衡，间接抑制IL-17分泌，而且抑制气道上皮细胞分泌CXCL1进而调控中性粒细胞浸润。藉此，本项目利用HDM和Papain哮喘小鼠模型，在哮喘不同阶段敲除pDC，结合体外细胞功能实验，明确pDC调控中性粒细胞浸润的关键细胞分子机制，为重症哮喘的治疗提供新策略。

Severe steroid-resistant asthma is the main cause of death associated with asthma. Airway damage caused by neutrophilic airway infiltration is the typical pathological characteristics of asthma. Recent studies uncovered a new role for plasmacytoid dendritic cell (pDC) in development of asthma. However, it is unknown whether neutrophilic airway inflammation is associated with pDC. Our study shows that the pDC knockout asthma mice induced by house dust mite (HDM) or papain increased the airway infiltration with neutrophils in both sensitized and challenged phases, and pDCs highly expressed TGF-β1 were accumulated in lung of asthmatic mice. Transfusion with pDCs in challenged phase could rectify the balance of Treg and Th17 in lungs of asthmatic mice. Furthermore, TGF-β1 could suppress CXCL1 expression and secretion by airway epithelial. Thus, we presume that pDCs not only rectify the balance of Treg and Th17 leading to suppression of IL-17 indirectly, but also inhibit CXCL1 expression and secretion by airway epithelial which regulates the neutrophils infiltration in lungs. Therefore, we used experimental asthma models induced by HDM and papain to investigate the role of pDCs and pivotal mechanism in regulation of airway neutrophil infiltration among different phases of asthma based on knockout pDC method and experiments in vitro. Our study will propose the new therapeutic strategy for severe asthma.