转录因子E2F1除参与调节细胞周期和细胞凋亡外，基因敲除鼠表现出更低的免疫耐受和更高的肿瘤发生，特别是自发淋巴细胞瘤比例较高，提示E2F1可能在免疫细胞的成熟发育和免疫应答上起到重要的作用。本实验室前期研究首次发现并报道了转录因子E2F1在树突状细胞成熟过程中起到反馈调节，防止树突状细胞过度活化的作用。本研究拟在此基础上，以基因敲除鼠为模型，围绕E2F1对细胞多个主要信号通路的调控和影响，深入研究和揭示转录因子E2F1反馈调节DC成熟的分子机制，系统阐述E2F1调控DC发育和分化的新功能，及其在免疫反应中的可能作用。本研究除有可能揭示细胞信号网络相互作用、维持稳态的分子机制，还可能对自身免疫性疾病的发生和发展提供线索。

Transcription factor E2F1 has been largely studied as a regulator in the cell cycle and apoptosis. The E2F1 gene knockout mice showed more frequently tumorigenesis and impacted immune tolerance, suggested that it may play an important role in immune development and responses to infections and particularly in tumorigenesis. Our previous study demonstrated first time that E2F1 served as a negative feedback signal during dendritic cell (DC) maturation to prevent DC over response.To further investigate the mechanisms of this feedback regulation of E2F1 on DC maturation and the extended function on DC development and differentiation, E2F1 gene knockout mice will be employed to elucidate this negative feedback signaling network.This study is expected to undercover the molecular network and mechanisms of signals maintaining DC homeostasis, as well as may proviede insight information on understanding autoimmune diseases.