Treg细胞基于Amphiregulin/EGFR机制发挥非免疫作用促进TBI后海马新生神经元功能成熟的研究

如何促进新生细胞分化成熟为有功能的神经元是成体神经干细胞（NSCs）修复颅脑创伤（TBI）的关键问题。过去认为Treg细胞通过免疫抑制机制发挥作用；新近研究发现Treg细胞还可影响干细胞和组织再生修复，但Treg细胞对TBI后成体神经再生的作用尚不清楚。本课题以挖掘Treg细胞独立于免疫抑制之外的促再生新机制为出发点，在前期一系列研究结论的基础上，调控Treg细胞浸润动力学使其高峰期与分化成熟关键期相吻合；在临床病例分析基础上，利用TBI模型和ere转基因小鼠探讨Treg细胞基于Amphiregulin/EGFR机制直接促进新生神经元功能成熟的作用；并利用体外细胞和脑片培养的非免疫微环境，进一步证实促再生作用并不依赖于免疫抑制。本课题以TBI病理进程原有的免疫细胞亚群为靶点，探寻可借助促再生直接作用和免疫抑制间接作用的综合调控措施，将有助于实现成体干细胞研究在TBI的临床转化。

How to promote newborn cells differentiating into mature and funtional neurons is the key problem in adult neural stem cells (NSCs) to repair the neurological function after traumatic brain injury (TBI). It has been agreed that the role of T cell subgroup Treg cells is mainly through the mechanism of immunosuppression. Recent studies have found that Treg cells can also affect the stem cells and tissues repair. However, the effect and mechanism of Treg cells on the regeneration of adult neurogenesis after TBI are still elusive. The purpose of this study is to explore a new mechanism for promoting regeneration of Treg cells independent of immunosuppression. The peak of infiltration kinetics of Treg cell is regulated to coincide with the critical stage of differentiation and maturation which has confirmed on the basis of previous research conclusions. Based on the analysis of clinical cases, TBI model and ere transgenic mice are used to study the role of Treg cells in directly promoting the functional maturation of newborn neurons through mechanism of Amphiregulin/EGFR pathway. Meanwhile, the nonimmune microenvironment of cells and brain slices culture in vitro is used to further demonstrate that the effect of regeneration is not dependent on the immunosuppression. In this study, the immune cell subgroup in TBI pathology is adopted as the regulatory targets, and a comprehensive measure by both directly promoting regeneration and indirect immunosuppression is established, which is more conducive to the clinical transformation of adult stem cells research in TBI.