HCV治疗中PD-1/PD-L1信号免疫调控作用的研究概况

肖雯; 裴家平; 季晓伟; 石丽萍; 邓小昭; 蒋龙凤; 张锦海; 王长军

doi:10.16462/j.cnki.zhjbkz.2017.02.023

HCV治疗中PD-1/PD-L1信号免疫调控作用的研究概况

doi: 10.16462/j.cnki.zhjbkz.2017.02.023

1. 中国药科大学生命科学与技术学院微生物与生化药学系, 江苏南京 210009;
2. 南京医科大学基础医学院生物化学与分子生物学系, 江苏南京 210029;
3. 南京军区疾病预防控制中心疾病预防控制所, 江苏南京 210002;
4. 南京医科大学第一附属医院感染病科, 江苏南京 210029

基金项目:

国家自然科学基金项目（81573213，81172724）；江苏省自然科学基金项目（BK20151089）

详细信息

作者简介:
肖雯(1989-),女,江苏南京人,在读硕士研究生。主要研究方向:病毒性肝炎发病机制。

中图分类号: R181.26
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出版历程
- 收稿日期: 2016-08-20
- 修回日期: 2016-11-08

An overview of immunoregulatory roles of PD-1/PD-L1 in HCV treatment

1. Department of Microbiology and Biochemical Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China;
2. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China;
3. Institute of Disease Control and Prevention, Center for Disease Control and Prevention of Nanjing Command, Nanjing 210002, China;
4. Department of Infection, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

摘要

摘要: 丙型肝炎病毒（hepatitis C virus，HCV）感染以其高慢性化、高肝纤维化和高肝细胞癌发生率，已经成为一个全球性的公共卫生问题。本综述拟概述HCV感染和治疗、PD-1（programmed cell death 1 gene，PD-1）高表达与免疫应答在HCV感染中的关联。在抗-HCV治疗中，提高免疫细胞调控能力是决定治疗效果的关键因素之一。慢性HCV感染中，有功能障碍的HCV特异性CD8⁺ T细胞上PD-1表达水平升高，阻断PD-1/PD-L1（programmed death-ligand 1，PD-L1）信号后，T细胞调控功能部分恢复；PD-1/PD-L1信号的增强，不仅抑制细胞毒性T细胞的功能，还影响CD8⁺T细胞的分化。临床上，阻断PD-1/PD-L1信号通路后，抗-HCV免疫应答水平增强。因此，加强对HCV感染诱导PD-1高表达的机制和HCV特异性T细胞功能障碍发生的机制研究，将有助于促进慢性HCV感染的预防性和治疗性疫苗的研发，并最终改善HCV治疗的效果。
- 肝炎抗体,丙型 /
- 免疫 /
- 信号传导
Abstract: As with high incidence of chronicity, hepatic fibrosis and hepatocellular carcinoma (HCC), hepatitis C virus (HCV) infection has become global problems of public hygiene. How to enhance the immunoregulatory ability of immunocytes turned out to be one of the key factors influencing the results of anti-HCV therapy. This review will summarize the survey of HCV infection and therapy, the association of PD-1 with anti-HCV immune response, and the roles of PD-1/PD-L1 blocking in anti-HCV. In chronic HCV patients, PD-1 level on dysfunctional HCV-specific CD8⁺ T cells was increased, and the virus-induced T cell dysfunction could be partly restored by PD-1/PD-L1 blocking. In HCV infection, the increased PD-1/PD-L1 inhibitory signal participates in the CTLs inhibition and CD8⁺T cell differentiation. It's also reported in clinically that anti-HCV immune response could be enhanced by PD-1/PD-L1 blocking. Therefore, it's of great importance to explore the mechanisms of HCV-induced PD-1 increasing and PD-1/PD-L1 inhibitory signal induced T cell dysfunction, which will contribute to the prophylactic and therapeutic vaccines for HCV infection, and lastly better HCV therapy.
- Hepatitis C antibodies /
- Immunity /
- Signal transduction