Frequency and Phenotype of Human Circulating and Intrahepatic Natural Killer Cell Subsets Is Differentially Regulated according to Stage of Chronic Liver Disease
Frequency and Phenotype of Human Circulating and Intrahepatic Natural Killer Cell Subsets Is Differentially Regulated according to Stage of Chronic Liver Disease
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DOI：
10.1159/000350821
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发表时间：
2013-06
期刊：
影响因子：
3.2
通讯作者：
H. Zimmermann;Jan Robert Mueller;S. Seidler;T. Luedde;C. Trautwein;F. Tacke
中科院分区：
文献类型：
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作者：
H. Zimmermann;Jan Robert Mueller;S. Seidler;T. Luedde;C. Trautwein;F. Tacke
背景/目的：实验性肝损伤模型表明，自然杀伤（NK）细胞是炎症和纤维化的关键调节因子。然而，肝脏疾病患者NK细胞及其亚群的数据有限。因此，我们全面表征了不同病因和纤维化阶段的慢性肝病（CLDs）患者的外周和肝脏NK细胞亚群。研究方法：在189名CLD患者（71名非肝硬化，118名肝硬化）和153名健康对照者的血液和肝活检（n = 40）中，通过FACS表征NK细胞和其他淋巴细胞群体。结果：与其他淋巴细胞亚群相比，CLD患者循环NK细胞普遍减少。纤维化患者血液中CD 16- NK细胞和肝脏中CD 16 + NK细胞亚群明显增加。肝硬化患者总体淋巴细胞减少，包括外周NK细胞减少。在胆汁淤积性和自身免疫性CLD中发现血液和肝脏中NK细胞亚群的最显著变化。血NK细胞及其亚群与肝功能相关，与纤维化标志物和炎性细胞因子呈负相关。结论：人类NK细胞与疾病严重程度的密切相关性以及CD 16 + NK细胞在早期纤维化中的肝内积累支持了肝纤维化中有益NK细胞功能的概念。
Background/Aims: Experimental liver injury models have indicated that natural killer (NK) cells are critical regulators of inflammation and fibrosis. However, data on NK cells and subsets in patients with liver diseases are limited. We thus comprehensively characterized peripheral and hepatic NK cell subsets in patients with chronic liver diseases (CLDs) of different etiologies and fibrosis stages. Methods: NK cells and other lymphocyte populations were characterized by FACS in 189 CLD patients (71 non-cirrhosis, 118 cirrhosis) and 153 healthy controls in blood and liver biopsies (n = 40). Results: In contrast to other lymphocyte subsets, circulating NK cells were generally reduced in CLD patients. Patients with fibrosis displayed a distinct increase of CD16- NK cells in blood and of the CD16+ NK cell subset in liver. Patients with cirrhosis had overall lymphopenia, including reduced peripheral NK cells. Most pronounced shifts in NK cell subsets in blood and liver were found in cholestatic and autoimmune CLDs. Blood NK cells and subsets correlated with liver function, and inversely with fibrosis markers and inflammatory cytokines. Conclusions: The close association of human NK cells with disease severity and the intrahepatic accumulation of CD16+ NK cells in early fibrosis favor the concept of beneficial NK cell functions in hepatofibrogenesis.