细胞周期调控蛋白NPAT对Treg细胞的功能调控及在自身免疫性疾病的作用和机制研究

在机体免疫耐受调控的复杂网络中，Treg细胞作为主要的免疫调控T细胞扮演了重要角色。而Treg细胞在生理状态下维持其数量平衡及功能稳态的调控机制，及其对免疫系统耐受的作用还未被充分揭示。NPAT蛋白是一种细胞周期调控蛋白，细胞生物学研究证实NPAT是一个“细胞周期加速分子”。申请人所在课题组曾对NPAT蛋白在T细胞发育早期及外周T细胞的增殖调控作用与机制开展研究，发现NPAT蛋白对胸腺发育阶段和外周T细胞的快速增殖过程都具有重要的调控作用。本项目拟通过构建Treg细胞条件性敲除Npat的小鼠品系，对NPAT调控Treg细胞稳态及功能的作用机制开展研究，揭示NPAT蛋白介导的Treg细胞快速增殖在自身免疫调控过程中的作用与机制，探讨Treg细胞稳态平衡的调控方式，并结合NPAT蛋白对Tcon细胞的调控作用的研究结果，探讨Treg细胞功能缺陷所致的自身免疫病的潜在治疗策略。

In the complex network of immune tolerance regulation, Treg cells, as the main immune regulatory T cells, play important roles. The intrinsic regulatory mechanism of Treg cells to maintain its quantity balance and function homeostasis in physiological state, and its role in immune system tolerance have not been fully revealed yet. NPAT protein is a cell cycle regulator. Cell biology studies have confirmed that NPAT is a cell-cycle accelerating factor. The applicant's research group has carried out researches on the regulatory effect and mechanism of NPAT protein on the proliferation of T cells both in the early stage of T cell development and peripheral T cells. We found that NPAT protein has an important regulatory role in the rapid proliferation T cells both in thymus development stage and peripheral T cells. This project aims to study the regulatory mechanism of NPAT on Treg cell homeostasis and immune regulatory function through the construction of NPAT conditional knockout mice of Treg cells. We plan to reveal the role and mechanism of the rapid proliferation of Treg cells mediated by NPAT protein in the process of autoimmune regulation, and explore the intrinsic regulatory mechanism of Treg cell homeostasis balance. By combining with the research results of the regulatory effect of NPAT protein on Tcon cells, we will try to explore the potential therapeutic strategies for autoimmune diseases caused by Treg cell dysfunction.