新生期小鼠肝脏CD4+Foxp3+调节性T细胞的特点和生理意义

调节性T细胞（Treg，CD4+Foxp3+）是维持免疫耐受和免疫自稳、调节免疫应答的专职T细胞亚群。Treg在生理和病理条件下以及不同组织中，具有独特的特点和功能。前期工作中我们发现新生期小鼠（1-2周龄）的肝脏中聚集有较高比例的Treg。与脾Treg相比，肝Treg中的活化细胞更多，增殖和凋亡水平更高，抑制T细胞增殖的能力更强。肝Treg的活化依赖MHC II所呈递的抗原肽。基于此，本项目将从1-2周龄小鼠肝Treg的特征性表达分子、Treg所识别抗原的种类、细胞的迁移/转归以及对炎症/免疫应答的抑制作用等方面着手，探讨新生期小鼠Treg在肝脏中聚集和活化的生理意义，探讨其在新生期外周免疫耐受、抑制炎症和促进肝脏成熟中的作用。研究结果将为深入理解Treg在新生期免疫耐受和免疫自稳中的调控机制和意义提供线索，为免疫相关疾病的治疗以及选择性地打破肝脏免疫耐受提供新的思路、方法和理论基础。

Regulatory T cells (Treg, CD4+Foxp3+) are essential in regulating immune tolerance, homeostasis, and immune responses. Under different physiological and pathological conditions, Tregs in various tissues have unqiue properties and functions. We previously found that Tregs in newborn mice accumulated in the liver during the first and second week after birth. Compared to splenic Tregs, liver Tregs had more activated cells, upregulated cell proliferation and cell death, and enhanced inhibitory capability. Peptide/MHC II complexes were required for liver Treg activation. Based on these results, we hypothesize that the accumulation of Tregs in the liver play a crucial role in immune tolerance and suppression of inflammation, thus promoting the functional maturation of the liver in newborn mice. In this proposal, we will investigate the physiological significance of Treg accumulation in the liver of newborn mice. We will focus on characterizing the molecules uniquely expressed in liver Tregs. We will also study the antigens that activate liver Tregs, the migration/differentiation of liver Tregs, and suppression of inflammation and immune responses by liver Tregs. The results will promote a better understanding of immune tolerance and homeostasis. It will also shed light on better design of therapeutic approaches for immune-related diseases.