特发性肺纤维化（IPF）的发生受免疫机制调控。申请者曾发现Treg细胞通过调节纤维细胞分化、迁移和分泌功能而参与肺纤维化的发生。iTR35细胞是一种新型Treg细胞，IL-35是iTR35等Treg细胞分泌的发挥免疫调节作用的最重要细胞因子，新近研究发现IL-35参与组织纤维化的发生，但在IPF中的作用未见研究。申请者初步观察到IPF患者外周血iTR35细胞数量和血浆IL-35水平下降。纤维细胞的分化、迁移等受IL-12的调节，而IL-35属于IL-12家族，故推测iTR35等Treg细胞可能通过分泌IL-35调节纤维细胞分化、迁移和分泌功能而参与肺纤维化的发生。本研究拟利用IPF患者和肺纤维化小鼠模型，通过体外共培养和动物模型体内干预等技术，探讨iTR35等Treg细胞是否通过分泌IL-35调节纤维细胞分化、迁移和分泌功能而参与IPF的发生，以期为IPF的治疗寻找新的靶点和方法。

Idiopathic Pulmonary Fibrosis (IPF) is a kind of chronic lung disease for which there is limited cure and whose etiopathogensis and pathogenesis are not clear. Its pathogenesis is regulated by immune mechanisms. We have found that Foxp3+ T regular (Treg) cells take part in the pathogenesis of lung fibrosis by promoting the differentiation, migration and secretion of fibrocytes. If iTR35 cells, this new kind of Foxp3- Treg cells take part in the pathogenesis of IPF is not clear. IL-35 is the key cytokine produced by iTR35 cells and Foxp3+ Treg cells. Some scientists found that it might take part in the pathogenesis of tissue fibrosis but it has not been studied in IPF. We found lower level of iTR35 cells and IL-35 in the peripheral blood and serum of IPF patients compared to the healthy control. The differentiation and migration of fibrocytes could be regulated by IL-12 and IL-35 belongs to IL-12 family. So we presume that iTR35 cells and Foxp3+ Treg cells might take part in the pathogenesis of lung fibrosis by regulating the differentiation, migration and secretion of fibrocytes through IL-35. We aim to detect the number and the percentage of iTR35 cells, Foxp3+ Treg cells, fibrocytes and the level of IL-35 in the IPF patients and lung fibrosis mouse model. We will co-culture the iTR35 cells and fibrocytes, Foxp3+ Treg cells and fibrocytes, IL-35 and fibrocytes in order to detect the effect of iTR35 cells, Foxp3+ Treg cells and IL-35 to the differentiation, migration and secretion of fibrocytes. We will also detect the effect of iTR35 cells, Foxp3+ Treg cells and IL-35 to lung fibrosis and fibrocytes in the lung fibrosis mouse model. Our aim is to clarify if iTR35 cells and Foxp3+ Treg cells take part in the pathogenesis of IPF by regulating the differentiation, migration and secretion of fibrocytes through IL-35 and try to find new therapy methods for IPF.