血吸虫致病主要是虫卵沉积诱发主的肝、肠等脏器肉芽肿病变并继发肝纤维化。其本质是CD4+T淋巴细胞对虫卵不断产生抗原的持续免疫应答。本课题组在前期系列研究中已证明ICOSL/ICOS信号可介导血吸虫致病期Th亚群(Th1/Th2/Th17/Tfh)极化并调节疾病进程。Th9是近年新发现的Th亚群。前期研究发现在感染血吸虫小鼠体内阻断Th9功能因子IL-9可减轻肝纤维化且Th9细胞上ICOS的表达呈显著上调。据此，提出科学假设“Th9细胞的极化参与了日本血吸虫病免疫病理的调节，调控Th9细胞的极化可能是控制肝纤维化发生和发展的新途经”。本项目应用ICOS-Tg/ICOSL-KO小鼠建立血吸虫病动物模型，体内外实验结合阐明调控ICOSL/ICOS信号通路对Th9极化并介导血吸虫病肝纤维化形成的分子机制，探讨Th9与其他Th亚群不同的免疫应答特征等重要科学问题，为血吸虫病肝纤维化的防治提供新思路。

The mainly pathogenesis of schistosomiasis is the occurrence of egg granulomas in the liver and intestine, and can result in more severe liver fibrosis. In essence, antigen secreted by schistosome eggs induced continuous immune response of CD4+T cell. Our seminar in earlier research find that ICOSL/ICOS signal play a key role in the polarization of Th1, Th2, Th17 cells and Tfh cells and process of schistosomiasis. Th9 cells are a new subset of Th cells. Studies have confirmed that neutralization of IL-9, which is the functional factor of Th9 cells, could ameliorate hepatic fibrosis in mice infected with Schistosoma japonicum. We also find that the proportion of ICOS+cells in Th9 cells markedly improved. Therefore, we can conjecture: Th9 polarized immune response to schistosome involve in mediation of immunopathogenesis in schistosomiasis and regulation of Th9 polarization may be a new way to control teh development of hepatic fibrosis. This project intends to establish ICOS transgenic (ICOS-Tg) mice and ICOSL knockout (ICOSL-KO) mice as experimental animal models for schistosomiasis. To elucidate how ICOSL/ICOS signal pathway contributes to Th9 polarization and the molecular mechanism of Th9-mediated liver fibrosis formation. In addition, to investigate the different immune response characteristics between Th9 and other Th subsets. This project will be expected to explore a new effective way for prevention and treatment of hepatic fibrosis.