Intrahepatic NK cells function suppressed in advanced liver fibrosis
Intrahepatic NK cells function suppressed in advanced liver fibrosis
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DOI：
10.1111/eci.12669
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发表时间：
2016-10-01
影响因子：
5.5
通讯作者：
Gao, Zhiliang
中科院分区：
文献类型：
--
作者：
Li, Xiaoyan;Zhang, Min;Gao, Zhiliang
背景：尽管大量流行病学研究表明乙型肝炎病毒相关性肝纤维化（HBV-LF），特别是肝硬化，是肝癌发展的主要危险因素，但决定纤维化持续性和肝癌发病机制的机制仍然不明确。很少有研究调查NK细胞在HBV-LF不同阶段的状态。方法从中山大学医学中心肝癌手术的32例hbv感染患者同时采集离肿瘤部位至少3cm的银组织和外周血。用流式细胞术检测NK细胞的数量，分析NK细胞的表型和功能。结果我们发现早期和晚期HBV-LF之间循环和肝内NK细胞的数量没有差异。然而，在晚期HBV-LF患者中，NKp46在肝内NK细胞上的表达下降，肝内NK细胞中IFN-和穿孔素的产生明显下降。结论在本研究中，我们发现在晚期HBV-LF患者中，NKp46在肝内NK细胞上的表达以及肝内NK细胞IFN-和穿孔素的产生均显著降低。这些结果表明，晚期HBV-LF患者肝内NK细胞的免疫功能明显受到抑制，这为NK细胞在纤维化持续和肝硬化后HCC发生中的潜在作用提供了新的认识。
BackgroundAlthough numerous epidemiological studies indicate that hepatitis B virus-related liver fibrosis (HBV-LF), particularly cirrhosis, represents the main risk factor for liver cancer development, the mechanisms determining the persistence of fibrosis and liver cancer pathogenesis are still poorly defined. Few studies have investigated the status of NK cells during different stages of HBV-LF.MethodsLiver tissues at least 3 cm away from the tumour site and peripheral blood were obtained simultaneously from 32 HBV-infected patients undergoing surgery for HCC at the medical centre of Sun Yat-sen University. We detected the amount of NK cells and analysed the phenotype and function of NK cells by flow cytometry.ResultsWe found that there was no difference in the amount of circulating and intrahepatic NK cells between early and advanced HBV-LF. However, NKp46 expression on intrahepatic NK cells decreased and productions of IFN- and perforin of intrahepatic NK cells declined apparently in patients with advanced HBV-LF.ConclusionIn the present study, we displayed that in patients with advanced HBV-LF, the expression of NKp46 on intrahepatic NK cells as well as productions of IFN- and perforin of intrahepatic NK cells decreased significantly. These results indicated that the immune function of intrahepatic NK cells in patients with advanced HBV-LF was suppressed distinctly, which provided new insight into the potential role of NK cells in the persistence of fibrosis and into the occurrence of HCC following cirrhosis.