幽门螺杆菌（H.pylori）感染诱导CD4+T细胞主要分化成分泌IFN-γ的Th1细胞，抵御病原菌的入侵。已有研究表明Notch信号参与Th1细胞的分化，申请人推测Notch信号参与调控H.pylori感染诱导的CD4+T细胞向Th1细胞的分化并进行了预实验。结果显示，H.pylori感染者CD4+T细胞mRNA与未感染者相比发生变化，生物信息学分析发现改变与多种T细胞激活的信号通路相关，包括Notch信号。H.pylori感染者CD4+T细胞Notch1及其下游靶基因Hes-1、T-bet和IFN-γ的mRNA表达均高于未感染者，并且T-bet和IFN-γ的表达与Notch1的表达成正相关，提示Notch信号被激活和参与Th1细胞分化。本课题拟在前期工作基础上，在体内外和转基因鼠探讨Notch信号在H.pylori感染诱导Th1细胞分化中的调控作用，为以Notch为治疗靶点提供新思路。

Helicobacter pylori (H.pylori) infection induces the differentiation of CD4+T cells into IFN-γ-producing Th1 cells，which plays a crucial role in the immune eradication of pathogen. However, the mechanistic details underlying this differentiation process remain unclear.. There is accumulating evidence showing that Notch signaling plays an important role in regulating the differentiation of naïve CD4+ T cells into Th1 subset，which has been proved in some infectious disease. Therefore, we put forward our hypothesis that Notch signaling might be initiated and activated during H.pylori infection and then subsequently regulates the differentiation of CD4+T cells into Th1 cells. Our preliminary experiment showed that the expression pattern of CD4+ T cell mRNA in H.pylori-infected patients differed from that in non-infected subjects. By bioinformation analysis, this change was associated with various T cell activating signal pathways, including Notch signal pathway. In addition, the mRNA expression of Notch1 and its downstream target gene Hes-1 in CD4+T cells of H.pylori-infected patients was higher than that in non-infected subjects，suggesting that Notch signaling was activated in host defense against H.pylori infection. The mRNA expression of key transcription factor T-bet and signature cytokine IFN-γ of Th1 cells was up-regulated in CD4+ T cells of H.pylori-infected patients compared with that in non-H.pylori-infected subjects. Moreover, the mRNA expression of T-bet and IFN-γ were both positively correlated with the mRNA expression of Notch 1 in H.pylori-infected patients, suggesting that Notch signaling was involved in the differentiation of Th1 cells... To our knowledge, there has been no previous work reported on the role of Notch signal pathway in the differentiation of CD4+T cells into Th1 effector cells during H.pylori infection. In this project, the aim is to investigate which Notch receptor as well as the ligand contributes to the differentiation of IFN-γ-secreting Th1 cells in this process by using modern molecular and cellular technologies, in vitro and in vivo experiments and mouse models. This study will provide insight into the role of Notch signaling in the differentiation of CD4+ T cells into Th1 cells during H.pylori infection and facilitate the development of exploiting Notch signaling as potential therapeutic targets for modifying and controlling the immune response against H.pylori infection.