Department of Clinical Laboratory Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
Intensive Care Unit, 964th Hospital of PLA, Changchun, China.
Viral Immunol. 2021 May;34(4):273-283. doi: 10.1089/vim.2020.0311. Epub 2021 Feb 26.
CD100 is an important immune semaphorin that is a secreted and membrane bound protein involved in infectious diseases. However, CD100 expression profile and the regulation to innate immune system in hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) was not previously reported. The aim of this study was to investigate CD100 level and modulatory function of CD100 to CD14 monocytes in HBV-ACLF patients. Plasma-soluble CD100 (sCD100) level and membrane-bound CD100 (mCD100) expression on peripheral CD14 monocytes was analyzed in HBV-ACLF patients. CD14 monocytes-induced cytotoxicity and CD14 monocytes-mediated T cell activation in response to CD100 stimulation was also assessed in direct and indirect contact coculture culture systems. HBV-ACLF patients had lower plasma sCD100 and higher mCD100 level on CD14 monocytes compared with asymptomatic HBV carriers, chronic hepatitis B patients, and controls. CD14 monocytes from HBV-ACLF patients induced limited target Huh7.5 cell death and secreted less interferon- (IFN-), tumor necrosis factor- (TNF-), and granzyme B in both direct and indirect contact coculture systems compared with controls. Recombinant sCD100 not only enhanced CD14 monocytes-mediated Huh7.5 cell death and granzyme B secretion, but it also elevated CD14 monocytes-induced IFN-/interleukin-17 production by CD4 T cells as well as IFN-/TNF- secretion by CD8 T cells in HBV-ACLF patients. The current data indicated that severe inflammation induced sCD100/mCD100 imbalance to inactivate CD14 monocytes response, which might be beneficial for the survival of HBV-ACLF patients.
CD100 是一种重要的免疫信号素，作为一种分泌型和膜结合蛋白，参与多种传染性疾病。然而，CD100 的表达谱及其对乙型肝炎病毒（HBV）相关慢加急性肝衰竭（ACLF）固有免疫系统的调控作用尚未见报道。本研究旨在探讨 CD100 在 HBV-ACLF 患者中的水平及其对 CD14 单核细胞的调节功能。分析了 HBV-ACLF 患者外周血可溶性 CD100（sCD100）水平和外周血 CD14 单核细胞表面膜结合 CD100（mCD100）的表达。还在直接和间接接触共培养系统中评估了 CD14 单核细胞诱导的细胞毒性和 CD100 刺激后 CD14 单核细胞介导的 T 细胞激活作用。与无症状 HBV 携带者、慢性乙型肝炎患者和对照组相比，HBV-ACLF 患者的血浆 sCD100 水平降低，CD14 单核细胞上的 mCD100 水平升高。与对照组相比，HBV-ACLF 患者的 CD14 单核细胞在直接和间接接触共培养系统中诱导靶细胞 Huh7.5 细胞死亡的能力有限，且分泌的干扰素-（IFN-）、肿瘤坏死因子-（TNF-）和颗粒酶 B 较少。重组 sCD100 不仅增强了 CD14 单核细胞介导的 Huh7.5 细胞死亡和颗粒酶 B 的分泌，而且还增加了 CD14 单核细胞诱导的 CD4 T 细胞 IFN-/白细胞介素-17 的产生以及 CD8 T 细胞 IFN-/TNF-的分泌。这些数据表明，严重的炎症导致 sCD100/mCD100 失衡，使 CD14 单核细胞的反应失活，这可能有利于 HBV-ACLF 患者的生存。
