Foxp3-双荧光报告系统人源化小鼠模型的构建

Regulatory T cells (Treg) play an important role in establishing and maintaining immune tolerance. It is closely related with tumor genesis and development, but the investigations of the underlying mechanisms and significance have not got an unified conclusion. Now, an ideal animal model is needed, which has both a human immune system and a tracking system for human Treg in vivo studies. In our preliminary experiments, we used lentivirus to infect the hematopoietic stem cell, and developed humanized mouse models with Foxp3 regulation sequence and fluorescence marker. Only small group of cells were detected with fluorescence. It is suggested that the technology system used in our preliminary experiments has the potential feasibility. In this study, we will optimize and develop a lentiviral vector containing the Foxp3 regulatory sequence and dual fluorescent reporter system , and establish humanized mouse models with full human immune system functions and tracking marker for Treg study. It will provide both an animal platform to clarify the role and significance of regulatory T cells in tumor genesis and development, as well as new ideas for model-based anticancer drugs development.

调节性T细胞(Regulatory T cells, Treg)在建立和维持免疫耐受过程中发挥重要作用。它与肿瘤的发生、发展关系密切，但具体机制和意义尚无统一的结论。目前尚缺乏一个理想的小动物模型- - 既含有人免疫系统又同时能追踪人Treg，以用于上述内容的活体研究。本项目组在前期预实验中采用慢病毒感染造血干细胞的方法，构建了含有Foxp3调控序列和荧光标记的人源化小鼠模型，且在外周血中检测到低比例的荧光阳性细胞，提示上述技术体系用于建立Treg细胞研究模型具有潜在可行性。本研究拟在前期研究基础上，优化并构建含有Foxp3调控序列和双荧光报告系统的慢病毒载体，建立具有健全人免疫系统功能和示踪作用的人源化小鼠模型，用于Treg的研究，为阐明Treg在肿瘤发生、发展中的作用和意义提供动物平台，为基于此模型的抗肿瘤药物的研发提供新思路。