特发性肺纤维化是涉及炎症反应、肺损伤、免疫反应及纤维化等综合作用的复杂病理过程，是涉及多种细胞及分子网络的动态过程。特发性肺纤维化患者在相对稳定期或稳定期后会突然出现病情急性加重期，进展迅速，病死率高，预后极差，但急性加重的发病原因与机制尚不清楚。我们前期数据表明特发性肺纤维化急性加重后真菌感染率显著增高，是导致患者死亡的重要原因之一；且肺纤维化合并真菌感染动物模型病情显著加重；我们还发现Dectin-1及IL-17可能在IPF/AE-IPF合并真菌感染中起着重要作用。患者病情加重后免疫功能发生了哪些变化使得机体对真菌易感？机制如何？本项目将进一步从分子、细胞、动物模型及临床样本研究Dectin-1-IL-17通路调控IPF/AE-IPF合并真菌感染中天然免疫及适应性免疫调控的分子机制。该研究将不仅加深我们对特发性肺纤维化及急性加重的发病机制的了解，而且可为临床治疗提供理论及实验依据。

The pathogenesis of IPF is a complex process with continual injury, chronic inflammation and wound healing response. IPF has been described as a gradually progressive disease, characterized by steady worsening of symptoms, lung function, and gas exchange. More recently, it has been recongnized that some patients without end-stage fibrosis have an acute exacerbation of IPF (AE-IPF) involving a rapid progression of disease, rendering the clinical course of individual patient unpredictable as AE-IPF ofen results in respiratory failure and death.The mechanism of AE-IPF is still not clear. Our preliminary data show that infection rate of fungal is significantly increased after AE-IPF. When receiving fungal challenge, mice model of bleomycin-induced pulmonary fibrosis show acute exacerbation of inflammation and fibrosis. Dectin-1 and IL-17 may play an important role in acute exacerbation of IPF with fungal infection. How the IPF/AE-IPF patients' immune responses change? What's the mechanism of high sensitivity to fungal? In this study, we will investigate the molecular mechanisms of fungal infection in AE-IPF patients and bleomycin-induced fibrosis mouse model. Key molecular KO mice such as IL-17A-/- and Dectin-1-/- will be used to investigate the mechanism of fungal infection in AE-IPF. This study can provide more detailed and integrated understanding of the cellular and molecular mechanisms of idiopathic pulmonary fibrosis. It can help pave the way for effective therapeutics for this devastating and complex disease.