饲鸽者肺属于过敏性肺炎，随着病情进展相继出现肉芽肿和肺纤维化等炎症损伤，但其炎症损伤的演变机制尚不清楚。本课题组发现饲鸽者肺急性期Th1型细胞因子占优势，发生肺纤维化后Th2型细胞因子占优势，且存在B细胞参与及Notch信号通路表达异常。文献提示B细胞可抑制Th1型细胞因子，并通过Notch信号通路影响肉芽肿形成及肺纤维化发生。因此，提出假说：B细胞可能通过Notch信号通路调节Th1/Th2失衡参与饲鸽者肺炎症损伤的演变。本课题采用鸽子羽毛等脱落物制作过敏原冻干粉，构建大鼠动物模型、细胞学模型，用基因敲除技术/Breg过继回输干预B淋巴细胞，并用DAPT抑制Notch信号通路，研究饲鸽者肺患者不同病理时期B淋巴细胞亚群及Notch信号通路特点；阐明干预B淋巴细胞或抑制Notch信号通路影响饲鸽者肺Th1/Th2失衡、肉芽肿形成及肺纤维化的分子机制，为阻断过敏性肺炎的炎症损伤提供新靶点。

Pigeon breeders’ lung (PBL) is a form of hypersensitivity pneumonitis. With the progression of the disease granuloma and pulmonary fibrosis as well as other inflammatory injury appear gradually. However, the mechanism of its inflammatory damage evolution is not clear. We found that Th1 cytokine was dominant in acute stage, while Th2 cytokine predominated after pulmonary fibrosis. In different disease stages, inflammatory injury is manifested as B cells were involved in and abnormal expression of Notch signaling pathway. The literature indicated that B cells might play an immunomodulatory role by inhibiting Th1 cytokine and participate in the formation of granulomas by interacting with Notch signaling pathways. Therefore, a hypothesis is proposed that B cells may participate in the evolution of lung injury in PBL by regulating the imbalance of Th1 / Th2. In this project, the characteristics of B lymphocyte subsets and Notch signaling pathway in different pathological stages of pigeon breeders’ lung will be studied by making the allergen freeze-dried powder from pigeon feathers and other exfoliated materials, establishing the animal models and cytological models of rats , intervening B lymphocytes through knockout technology / Breg adoptive transfer，and intervening in the Notch signaling pathways through the relevant pathway inhibitor ( DAPT）. It will clarify the molecular mechanism of B cell influencing signal pathways,Th1/Th2 imbalance and pulmonary fibrosis by intervening B lymphocytes or inhibiting Notch signaling pathway in order to provide a new target for blocking the inflammatory injury of hypersensitivity pneumonitis.