慢性排斥所致的闭塞性细支气管炎（OB）是肺移植术后患者长期生存率低的主要原因。IL-17促进肺移植排斥反应的发生和发展。本课题组前期研究发现IL-17基因敲除后小鼠OB模型的病理改变明显减轻。IL-17家族成员IL-25负调控TH1和TH17细胞反应。IL-25受体表达于TH2和TH9细胞，因此，IL-25可能调节TH2和TH9细胞下调TH1和TH17细胞反应减轻肺移植术后OB。本研究拟在体外分化TH1，TH2，TH9和TH17细胞，流式细胞仪检测IL-25对TH1和TH17产生的影响，Western Blot检测IL-25R信号中磷酸化Act-1水平，并分析其在调节TH9产生IL-10中的作用。体内研究以IL-25基因敲除小鼠，重组IL-25干预OB的进展，明确IL-25促进TH9细胞产生IL-10,下调TH17细胞反应，减轻OB，为肺移植术后OB治疗提供重要的理论依据。

Obliterative bronchiolitis (OB) has been a major obstacle for long-term allograft survival after lung transplantation. IL-17 play a vital role in allograft rejection. Our previous study showed that IL-17 knock-out attenuate the pathology of trachea allograft. IL-25, a IL-17 family member, down-regulate the inflammatory responses and autoimmune disease by inhibiting TH1 and TH17 cells. IL-17RB, which is a key constituent of IL-25R, is expressed by TH2 and TH9 cells. Our hypothesis is IL-25 may promote the activation and function of TH2 cells to decrease TH1 and TH17 responses, as well as increase the IL-10 production by TH9 cells, thus down-regulate the chronic rejective responses after lung transplantation . In this project, we differentiate TH1，TH2，TH9 and TH17 cells in vitro and detect the expression of IL-17 and IFN-gamma by flow cytometry. Western blot determine the Act-1 phosphorylation and evaluate the role of IL-25 in promoting IL-10 production by TH9 cells. Wide-type and IL-25-/- mouse are used to evaluate the role of exogenous IL-25 in attenuating the development of OB in in-vivo experiment. Our study may provide a new strategy to improve the research development and clinical treatment of OB.