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-γ (IFN-γ), tumor necrosis factor-α (TNF-α), 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-γ/interleukin-17 production by CD4⁺ T cells as well as IFN-γ/TNF-α 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.

中文翻译：

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可溶性和膜结合 CD100 之间的不平衡调节乙型肝炎病毒相关的慢性急性肝衰竭中的单核细胞活性

CD100 是一种重要的免疫信号素，是一种与感染性疾病有关的分泌和膜结合蛋白。然而，CD100 表达谱和对乙型肝炎病毒 (HBV) 相关的慢加急性肝衰竭 (ACLF) 的先天免疫系统的调节以前没有报道。本研究的目的是研究HBV-ACLF 患者的 CD100 水平和 CD100 对 CD14 ^{+单核细胞的调节功能。}在 HBV-ACLF 患者中分析了外周 CD14 ⁺单核细胞上的血浆可溶性 CD100 (sCD100) 水平和膜结合 CD100 (mCD100) 表达。CD14 ⁺单核细胞诱导的细胞毒性和 CD14 ⁺还在直接和间接接触共培养系统中评估了响应 CD100 刺激的单核细胞介导的 T 细胞活化。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 较低，而 CD14 ^{+单核细胞上的 mCD100 水平较高。}在直接和间接接触共培养系统中，来自 HBV-ACLF 患者的CD14 ⁺单核细胞诱导有限的靶标 Huh7.5 细胞死亡并分泌较少的干扰素-γ (IFN- γ )、肿瘤坏死因子-α (TNF -α ) 和颗粒酶 B与对照相比。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 分泌，但它也提高了 CD14 ⁺单核细胞诱导的 CD4 ^{+ T 细胞产生的 IFN-} γ /白介素-17以及 CD8 ⁺ T细胞分泌的IFN- γ /TNF - α HBV-ACLF 患者的细胞。目前的数据表明，严重的炎症诱导 sCD100/mCD100 失衡，使 CD14 ⁺单核细胞反应失活，这可能有利于 HBV-ACLF 患者的生存。