最新证据表明, mTOR介导的自噬通路在调节T细胞分化及稳态方面具有重要意义。我们前期工作发现，高迁移率组蛋白-1(HMGB1)可显著上调慢乙肝患者CD4+T的自噬。激活的肝星状细胞(HSCs)是促肝纤维化的核心细胞，具有免疫学特性且可分泌HMGB1。因此,我们推测HSCs可通过HMGB1调控mTOR信号实现其对CD4+T自噬和分化的共同调节。本研究从体内外试验出发，体外应用western blot、透射电镜、mRFP-GFP-LC3荧光体系等方法综合评估肝纤维化进程中CD4+T的自噬水平，体内选择性沉默小鼠CD4+T的自噬相关基因Atg7的表达观察其对肝纤维化进程的影响，并采用蛋白质芯片及高通量流式细胞术分析HMGB1与mTOR在自噬通路中相互作用的具体分子机制。研究结果将为基于调节CD4+ T自噬水平的肝纤维化免疫治疗打下坚实理论基础。

Recent evidence has highlighted the role of mTOR-mediated autophagy pathway in T cell homeostasis and differentiation. Our previous data have demonstrated that high mobility group box 1 (HMGB1) significantly enhances peripheral CD4+ T autophagy during chronic hepatitis B virus (HBV) infection. Activated hepatic stellate cells (HSCs) are critical cells to enhance liver fibrosis progression, showing the immunological features and secreting HMGB1. Thus, we suppose HSCs may control both CD4+ T autophagy and differentiation by producing HMGB1 to influence mTOR pathway. In this study, the in vitro autophagic activity is to be assessed by western blot analysis, the transmission electron microscope and the mRFP-GFP-LC3 fluorescence system. Besides, we establish Atg7 f/f CD4-cre mouse models to investigate the exact effects of CD4+ T autophagy during liver fibrosis progression. Moreover, we utilize both the protein microarray and high-throughput flow cytometry analyses to detailed molecular mechanisms involved in the interactions between HMGB1 and mTOR mediated autophagic pathways. Data from this study could greatly contribute to the immunotherapy to treat liver fibrosis, based on regulating CD4+ T autophagy.