炎症免疫反应在结直肠癌发生发展中的双重作用，是结直肠癌研究领域的热点和难点。调节性T细胞（Treg）具有免疫抑制功能，参与调控饮食及肠道菌群引起的肠道炎症反应，而不同Treg亚群在肠炎诱导肠癌过程中的作用及机制有待阐明。我们前期发现缺失DBC1的Treg稳定性提高，同时具有更高免疫抑制活性和更好的组织稳定性，其具体机制需深入研究。我们通过制备Treg特异性敲除DBC1的小鼠，并构建肠炎诱导肠癌模型进行研究，发现缺失DBC1小鼠肠炎减轻，肠癌进展显著缓解；通过进一步研究，我们发现DBC1通过NF-kB信号通路调控Treg细胞OX40蛋白水平，进而调节Treg在炎症条件下的功能稳定性。本项目旨在利用分子生物学手段结合小鼠疾病模型，阐明炎性条件下DBC1通过NF-kB调控OX40的具体机制，探索DBC1缺失调控Treg阻止炎症驱动肠癌发生发展的分子机理，为肠炎驱动的肠癌临床治疗提供新策略。

The dual roles of inflammatory immune response in the development of colorectal cancer are the focus and great challenge in the field of colorectal cancer research. Regulatory T cells (Treg) are a subset of immunosuppressive T cells that are critical for homeostasis, participating in the regulation of inflammation caused by diet and intestinal microbiota. However, the role and mechanism of different Treg subsets in the process of colitis induced colorectal cancer still need to be elucidated. In our previous study, we found that the DBC1-deleted Treg has higher stability, more immunosuppressive activity and better tissue stability, but its mechanism needs further study. We constructed a new strain mice with DBC1 conditional knock out in Treg. In the following study, it was found that the enteritis symptoms of DBC1 deficient mice were alleviated and the progress of colorectal cancer was significantly relieved. In further studies, we found that DBC1 regulated OX40 protein level through NF-kB signaling pathway under inflammation conditions, thus participating in the regulation of Treg function. In the further studying, we will use molecular biological techniques combined with mouse disease model to elucidate the specific mechanism of DBC1 regulating OX40 by NF-kB signaling pathway under inflammatory conditions, and explore the molecular mechanism of DBC1-deficient Treg preventing the development of inflammatory driving colorectal cancer, so as to provide a new strategy for clinical treatment of colitis driving colorectal cancer.