自噬参与原发性胆汁性胆管炎患者Th17/Treg免疫失衡的研究  

Autophagy Participates in Th17/Treg Imbalance of Patients with Primary Biliary Cholangitis

作　　者：孙可帅 王璐[1] 李博[1] 刘雁声 田思远 张苗 马硕怡 周新民[1] SUN Ke-shuai;WANG Lu;LI Bo;LIU Yan-sheng;TIAN Si-yuan;ZHANG Miao;MA Shuo-yi;ZHOU Xin-min(State Key Laboratory of Cancer Biology,Xijing Hospital of Digestive Diseases,The Fourth Military University,Xi'an,Shaanxi,710032,China)

机构地区：[1]第四军医大学西京消化病医院肿瘤生物学国家重点实验室,陕西西安710032

出　　处：《现代生物医学进展》2020年第8期1410-1415,1424,共7页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81770569);中国博士后科学基金项目(2018M643871);国家重大新药创制项目(2014ZX09508002-001)。

摘　　要：目的:Th17/Treg免疫失衡在原发性胆汁性胆管炎(PBC)的发病机制中起到关键作用。自噬是调节T细胞稳态的重要环节。本研究旨在探索自噬对PBC患者Th17/Treg免疫失衡的影响。方法:选取20例初次诊断的PBC患者,20例健康对照者,收集其外周血单个核细胞(PBMCs)。利用流式细胞术检测PBC患者与健康对照者PBMCs中Th17和Treg细胞分布及其胞内自噬的水平,进一步体外利用氯喹抑制自噬,证实自噬对PBC患者Th17/Treg平衡的影响。结果:相较于健康对照者,PBC患者Th17细胞占CD4^+T比例上升(P<0.05),且血清中IL-17含量较高(P<0.01);Treg细胞比例下降(P<0.05),且血清中TGF-β含量较低(P<0.01)。而PBC患者Th17细胞和Treg细胞内自噬水平均升高。另外,体外实验结果证实,自噬抑制剂氯喹能够有效地恢复PBC患者PBMCs中Th17/Treg平衡。结论:异常活化的自噬可导致PBC患者Th17/Treg免疫失衡,抑制自噬能够在体外恢复此平衡。因此,对异常自噬的干预可能将成为PBC疾病治疗的新方法。Objective:Immune disorder plays a critical role in the pathogenesis of primary biliary cholangitis(PBC).Autophagy is a significant process to maintain the homeostasis of T cell.The purpose of this study was to investigate the effect of autophagy on Th17/Treg immune imbalance in patients with PBC.Methods:Twenty newly diagnosed patients with PBC,and twenty healthy controls were selected.And their peripheral blood mononuclear cells(PBMCs)were collected.We detected distribution and intracellular autophagy flux of Th17 and Treg cells of patients with PBC and healthy controls by flow cytometry.In addition,we demonstrated the effect of autophagy on Th17/Treg immune balance of patients with PBC in vitro.Results:Compared with healthy controls,patients with PBC had increased proportion of Th17 cells(P<0.05)and IL-17 in serum(P<0.01),while decreased Treg cells(P<0.05)and TGF-β(P<0.01).Both Th17 and Treg cells of patients with PBC exhibited activated autophagy.Additionally,the results in vitro confirmed that autophagy inhibitor chloroquine is able to restore Th17/Treg immune balance in patients with PBC.Conclusions:Abnormally activated autophagy contributed to Th17/Treg immune balance in patients with PBC,and inhibition of autophagy can restore this balance in vitro.Therefore,intervention in abnormal autophagy may be a new method for the treatment of PBC.

关 键 词：原发性胆汁性胆管炎 Th17 TREG 自噬 

分 类 号：R-33[医药卫生] R657.45