Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis
Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis
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DOI：
10.1016/j.jaut.2006.04.001
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发表时间：
2006-06-01
影响因子：
12.8
通讯作者：
Gershwin, M. Eric
中科院分区：
文献类型：
--
作者：
Chuang, Ya-Hui;Lian, Zhe-Xiong;Gershwin, M. Eric
虽然原发性胆汁性肝硬化（PBC）的发病机制仍然是个谜，免疫系统在病理的开始和随后的发展中起着关键作用。先前的研究表明先天免疫系统的关键作用。重要的是，自然杀伤（NK）细胞在肝脏中丰富，它们作为免疫系统的哨兵。此外，NK细胞基于其免疫调节细胞因子的产生而具有显著的生物活性。为了解决这一问题，我们研究了PBC患者以及正常和肝病对照组中NK细胞的几种定性和定量活性。我们在此报告PBC患者血液和肝脏NK细胞的频率和绝对数量显着增加。此外，PBC患者中分离的NK细胞的细胞毒活性和穿孔素表达显著增加，与血浆IL-8水平增加和NK细胞上CD 128 a（IL-8受体）的表达相关。相反，PBC患者NK细胞合成的IFN-γ、IL-6和IL-8水平与对照组相比显著降低。总之，本研究的数据提供了令人信服的证据，支持NK细胞在PBC免疫发病机制中的生物学作用。(c)2006爱思唯尔有限公司保留所有权利。
Although the pathogenesis of primary biliary cirrhosis (PBC) remains enigmatic, the immune system plays a key role in the initiation and subsequent development of pathology. Previous studies have indicated a critical role of the innate immune system. Importantly, natural killer (NK) cells are abundant in liver where they serve as sentinels of the immune system. In addition, NK cells have significant biologic activity based on their production of immumoregulatory cytokines. To address this issue, we have investigated several qualitative and quantitative activities of NK cells in patients with PBC as well as normal and liver diseased controls. We report herein a marked increase in the frequency and absolute number of blood and liver NK cells in PBC patients. Moreover, the cytotoxic activity and perforin expression by isolated NK cells were significantly increased in PBC patients associated with increased levels of plasma IL-8 and the expression of CD128a (IL-8 receptor) on NK cells. In contrast, the levels of IFN-gamma, IL-6 and IL-8 synthesized by NK cells were significantly decreased in PBC patients as compared to controls. In conclusion, data from this study provide compelling evidence supporting a biologic role of NK cells in the immunopathogenesis of PBC. (c) 2006 Elsevier Ltd. All rights reserved.