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1型天然淋巴细胞促成慢性乙型肝炎的发病机制。

Type 1 innate lymphoid cells contribute to the pathogenesis of chronic hepatitis B.

作者信息

Yang Zhiqing, Tang Tengqian, Wei Xiaolin, Yang Shuang, Tian Zhiqiang

机构信息

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.

出版信息

Innate Immun. 2015 Aug;21(6):665-73. doi: 10.1177/1753425915586074. Epub 2015 May 14.

DOI:10.1177/1753425915586074
PMID:25977358
Abstract

Innate lymphoid cells (ILCs) function in producing effector cytokines in response to pathogenic infections. However, the roles and related mechanisms of the ILC subpopulations, ILC1 and ILC2, which mirror Th1 and Th2 in adaptive immunity, remain unclear. In this study, we found the markedly elevated levels of the ILC1 transcription factor T-bet, the effector cytokine IFN-γ and the IL/receptor signaling molecules IL-12/IL-12R, which are indispensable for ILC1 differentiation, in the helper ILCs of chronic hepatitis B (CHB) patients. The elevated level of the ILC1 population was significantly associated with hepatic damage in CHB patients, and was not related to telbivudine treatment. In contrast, although we also observed elevated levels of ILC2-related factors, including IL-33, ST2, GATA3 and IL-13 in helper ILCs, the extent of elevation shown by each was lower than that shown by the ILC1-related factors. Furthermore, the activity of the ILC2s did not correlate with either HBV copies or liver damage. The findings of this study suggest potential pro-inflammatory roles for ILC1s in CHB pathogenesis, potentiating these cells and their related molecules as targets of diagnostic, prognostic and/or therapeutic strategies for hepatitis B.

摘要

固有淋巴细胞(ILC)在应对病原体感染时发挥产生效应细胞因子的功能。然而,在适应性免疫中与Th1和Th2相对应的ILC亚群ILC1和ILC2的作用及相关机制仍不清楚。在本研究中,我们发现慢性乙型肝炎(CHB)患者的辅助性ILC中,ILC1转录因子T-bet、效应细胞因子IFN-γ以及对ILC1分化不可或缺的IL/受体信号分子IL-12/IL-12R的水平显著升高。ILC1群体水平的升高与CHB患者的肝损伤显著相关,且与替比夫定治疗无关。相比之下,尽管我们也观察到辅助性ILC中ILC2相关因子水平升高,包括IL-33、ST2、GATA3和IL-13,但各因子的升高程度低于ILC1相关因子。此外,ILC2的活性与HBV拷贝数或肝损伤均无相关性。本研究结果提示ILC1在CHB发病机制中可能具有促炎作用,可将这些细胞及其相关分子作为乙型肝炎诊断、预后和/或治疗策略的靶点。

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