高度激活的TRAIL + CD56亮NK细胞与HBV-LC患者的肝损伤有关

StephenW

Highly activated TRAIL + CD56 bright NK cells are associated with the liver damage in HBV-LC patients
Yujie Jiang  1 , Shuang Qin  1 , Xin Wei  2 , Xiaoyuan Liu  3 , Jingjing Guan  1 , Hengyue Zhu  1 , Guolin Chang  3 , Yingxiao Chen  4 , Hong Lu  1 , Jingjing Qian  1 , Zhongyong Wang  1 , Mo Shen  5 , Xiangyang Lin  6
Affiliations
Affiliations

    1
    Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
    2
    Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
    3
    School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
    4
    Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, 325000, China.
    5
    Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
    6
    Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].

    PMID: 33515618 DOI: 10.1016/j.imlet.2020.12.008

Abstract

Background: Chronic hepatitis B-related liver cirrhosis(HBV-LC)is the most common cirrhosis in China, which is characterized as liver damage and high mortality. We aim to investigate the characteristics of TRAIL+NK cells in patients with HBV-LC and their relationship with liver damage in patients with HBV-LC.

Methods: Thirty cases each of chronic hepatitis B (CHB), HBV-related compensated liver cirrhosis (HBV-CLC) and HBV-related decompensated liver cirrhosis (HBV-DLC) patients were recruited in this study. Thirty age-and sex-matched healthy individuals were recruited as healthy controls (HCs). NK cell phenotypes were determined using flow cytometry. Serum chemokine concentrations were ascertained using the CBA Flex set. Cell apoptosis was analyzed using the Annexin V-PE/7-AAD apoptosis Kit.

Results: CD56bright NK cells increased, but CD56dim NK cells reduced in HBV-LC patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was mainly expressed on CD56bright NK cells. As the degree of liver damage increased, the frequency and activation of total TRAIL+NK cells and TRAIL+NK cell subsets continued to increase, especially in the HBV-LC patients. Furthermore, the difference in frequency and activation of total TRAIL+NK cells between the HBV-CLC and HBV-DLC groups was mainly due to the highly activation and increase of TRAIL+CD56bright NK cells. With the increasing degree of liver damage, CXCR3-associated chemokines (including CXCL9, CXCL10 and CXCL11) were constantly increased, particularly in the HBV-DLC group. The expression of CXCR3 on CD56bright NK cells was almost 100 % in all enrolled cohorts. CXCR3-associated chemokines were negatively correlated with liver function and positively correlated with fibrosis degree. TRAIL+CD56bright NK cells were negatively correlated with liver function, and positively correlated with fibrosis degree and CXCR3-associated chemokines. The apoptosis of K562 cells and hepatocytes was suppressed partially by the TRAIL-neutralizing antibodies.

Conclusions: The increase of CXCR3-related chemokines (including CXCL9, CXCL10 and CXCL11) might be related to the migration of TRAIL+ CD56bright NK cells to the liver. Highly activated TRAIL+ CD56bright NK cells were associated with the liver damage in HBV-LC patients. These findings may provide new perspectives and theoretical basis for future immunotherapy of HBV-LC patients.

Keywords: CD56(bright) NK cells; HBV-related liver cirrhosis; Liver damage; TRAIL.

Copyright © 2021. Published by Elsevier B.V.

StephenW

高度激活的TRAIL + CD56亮NK细胞与HBV-LC患者的肝损伤有关
姜玉杰1，双琴1，辛薇2，刘小元3，关晶晶1，朱恒跃1，郭林昌3，陈颖晓4，洪露1，晶晶前1，王忠勇1，莫申5，向阳林6
隶属关系
隶属关系

    1个
    温州医科大学附属第一医院检验科，温州325000。
    2
    安徽医科大学附属第一医院检验科，安徽合肥230032
    3
    温州医科大学检验医学与生命科学学院，温州
    4
    医科大学附属温州第一附属医院传染病科，温州325000。
    5
    温州医科大学附属第一医院检验科，温州325000。电子地址：[email protected]。
    6
    温州医科大学附属第一医院检验科，温州325000。电子地址：[email protected]。

    PMID：33515618 DOI：10.1016 / j.imlet.2020.12.008

抽象

背景：慢性乙型肝炎相关性肝硬化（HBV-LC）是中国最常见的肝硬化，其特征是肝损害和高死亡率。我们旨在调查HBV-LC患者的TRAIL + NK细胞的特征及其与HBV-LC患者肝损伤的关系。

方法：本研究招募了30例慢性乙型肝炎（CHB），HBV相关的代偿性肝硬化（HBV-CLC）和HBV相关的代偿性肝硬化（HBV-DLC）患者。招募了30个年龄和性别相匹配的健康个体作为健康对照（HCs）。使用流式细胞术确定NK细胞表型。使用CBA Flex套件确定血清趋化因子浓度。使用膜联蛋白V-PE / 7-AAD细胞凋亡试剂盒分析细胞凋亡。

结果：HBV-LC患者的CD56bright NK细胞增加，而CD56dim NK细胞减少。肿瘤坏死因子相关的凋亡诱导配体（TRAIL）主要在CD56bright NK细胞上表达。随着肝脏损害程度的增加，总TRAIL + NK细胞和TRAIL + NK细胞亚群的频率和激活持续增加，尤其是在HBV-LC患者中。此外，HBV-CLC和HBV-DLC组之间总TRAIL + NK细胞的频率和激活差异主要是由于TRAIL + CD56bright NK细胞的高度激活和增加。随着肝脏损害程度的增加，与CXCR3相关的趋化因子（包括CXCL9，CXCL10和CXCL11）不断增加，尤其是在HBV-DLC组中。在所有纳入的队列中，CD56bright NK细胞上CXCR3的表达几乎100％。 CXCR3相关趋化因子与肝功能呈负相关，与纤维化程度呈正相关。 TRAIL + CD56b明亮的NK细胞与肝功能呈负相关，与纤维化程度和CXCR3相关的趋化因子呈正相关。 TRAIL中和抗体部分抑制了K562细胞和肝细胞的凋亡。

结论：CXCR3相关趋化因子（包括CXCL9，CXCL10和CXCL11）的增加可能与TRAIL + CD56bright NK细胞向肝脏的迁移有关。高度激活的TRAIL + CD56bright NK细胞与HBV-LC患者的肝损伤有关。这些发现可能为HBV-LC患者未来的免疫治疗提供新的观点和理论依据。

关键词：CD56（亮）NK细胞； HBV相关性肝硬化；肝损害;落后。

版权所有©2021. Elsevier B.V.发行