MicroRNA-138通过靶向乙型肝炎病毒相关肝病患者的PD-1调节T细胞

StephenW

MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus-Related Liver Diseases
Wei Liu  1 , Xianzhao Zheng  1 , Jie Wang  2 , Quanli He  1 , Junmin Li  1 , Zengzeng Zhang  1 , Hongchun Liu  3
Affiliations
Affiliations

    1
    Department of Clinical Laboratory, The People's Hospital of Jiaozuo, China.
    2
    Department of Nephrology, The Affiliated Hospital of Henan Polytechnic University, China.
    3
    Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, China.

    PMID: 33410459 DOI: 10.1093/labmed/lmaa110

Abstract

Objective: T-cell exhaustion in hepatitis B virus (HBV) infection, which results from upregulation of programmed cell death-1 (PD-1), leads to persistent HBV infection and related disease progression. Therefore, agents targeting PD-1 may prove beneficial in the treatment of this condition. MicroRNA-138 (miR-138) possesses an anti-tumor ability in that it targets immune checkpoints, including PD-1. However, the function and underlying mechanisms of miR-138 in patients with HBV infection remains unclear.

Methods: Specimens were collected from healthy volunteers (n = 43) and patients with chronic hepatitis B (CHB; n = 52), liver cirrhosis (LC; n = 26), and hepatocellular carcinoma (HCC; n = 31); carriers of HBV who were asymptomatic (n = 51); and patients with CHB receiving antivirus treatment (n = 11). These specimens were then used to study the expression and relationship among miR-138, PD-1, and HBV DNA viral load. To investigate the role of miR-138 in regulating PD-1 expression and determine the effect of miR-138 in regulating T-cell function, a luciferase assay and a transfection assay were each performed with primary CD3+ T cells.

Results: We found that PD-1 was upregulated and miR-138 was downregulated in patients with CHB, LC, and HCC. Correlations analysis revealed that PD-1 expression was positively correlated with HBV DNA viral load whereas miR-138 was negatively correlated. Luciferase assay results showed that miR-138 directly inhibited PD-1 expression by interacting with the 3'-untranslated region of PD-1. As a result of miR-138 overexpression in primary T cells, PD-1 in these T cells was downregulated and antivirus cytokines secreted by T cells were significantly upregulated. In addition, the expression levels of PD-1 and miR-138 were reversed in patients with CHB who received antivirus treatments.

Conclusion: Results showed that miR-138 can promote T-cell responses within patients with HBV infection by inducing a PD-1 blockade. Such an effect suggests that miR-138 may serve as a new therapeutic target for the treatment of HBV infection.

Keywords: HBV-related liver diseases; PD-1; T cells; miR-138.

© American Society for Clinical Pathology 2021. All rights reserved. For permissions, please e-mail: [email protected].

StephenW

MicroRNA-138通过靶向乙型肝炎病毒相关肝病患者的PD-1调节T细胞功能
刘伟1，郑先昭1，王杰2，何全力1，李俊民1，张增增1，刘宏春3
隶属关系
隶属关系

    1个
    焦作市人民医院检验科。
    2
    河南工业大学附属医院肾内科
    3
    郑州大学第一附属医院临床实验室

    PMID：33410459 DOI：10.1093 / labmed / lmaa110

抽象

目的：乙型肝炎病毒（HBV）感染中的T细胞衰竭是由程序性细胞死亡1（PD-1）上调引起的，导致持续性HBV感染和相关疾病进展。因此，靶向PD-1的药物可证明对治疗这种疾病有益。 MicroRNA-138（miR-138）具有抗肿瘤能力，因为它靶向包括PD-1在内的免疫检查点。然而，miR-138在HBV感染患者中的功能和潜在机制仍不清楚。

方法：从健康志愿者（n = 43）和慢性乙型肝炎（CHB； n = 52），肝硬化（LC； n = 26）和肝细胞癌（HCC； n = 31）患者中收集标本。无症状的乙肝病毒携带者（n = 51）； CHB患者接受抗病毒治疗（n = 11）。然后将这些标本用于研究miR-138，PD-1和HBV DNA病毒载量之间的表达及其相互关系。为了研究miR-138在调节PD-1表达中的作用并确定miR-138在调节T细胞功能中的作用，对原发性CD3 + T细胞分别进行了荧光素酶测定和转染测定。

结果：我们发现CHB，LC和HCC患者PD-1上调，而miR-138下调。相关分析表明，PD-1表达与HBV DNA病毒载量呈正相关，而miR-138呈负相关。荧光素酶测定结果表明，miR-138通过与PD-1的3'-非翻译区相互作用直接抑制PD-1的表达。由于miR-138在原代T细胞中过度表达，这些T细胞中的PD-1被下调，而T细胞分泌的抗病毒细胞因子被显着上调。此外，接受抗病毒治疗的CHB患者PD-1和miR-138的表达水平逆转。

结论：结果表明，miR-138可以通过诱导PD-1阻断来促进HBV感染患者的T细胞应答。这种效果表明，miR-138可以作为治疗HBV感染的新治疗靶标。

关键词：HBV相关肝病； PD-1； T细胞； miR-138。

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