Ι型固有淋巴细胞对慢性乙型肝炎的作用及机制

Type Ⅰ innate lymphoid cells involve in the pathogenesis of chronic hepatitis B

目的初步探讨固有淋巴细胞(ILCs)亚群如ILC1和ILC2(分别为适应性免疫应答中Th1和Th2的映像)对病原体感染的作用机制。方法收集临床慢性乙肝(CHB)患者和健康对照外周血和肝组织,运用流式细胞术、定量PCR和ELISA方法,检测CHB患者中ILC1和ILC2的频率、Ⅰ型和Ⅱ型转录因子和细胞因子水平,并与CHB患者临床指标进行相关性分析。结果CHB患者总ILCs中,ILC1转录因子T-bet、效应细胞因子IFN-γ、ILC1分化相关信号通路分子IL-12/IL-12R水平均显著升高。升高的ILC1亚群频率与CHB患者肝损伤显著相关,但与替比夫定疗效无明显关联。虽然ILC2相关的转录因子、细胞因子等在CHB中也升高,但升高的幅度均低于ILC1细胞。而且,ILC2细胞活性与HBV拷贝或肝损伤均没有显著关联。结论本研究结果提示了ILC1在CHB病理过程中的潜在促炎作用,以及ILC1及其相关分子可能是CHB诊断、预后甚至治疗的潜在干预靶标。

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 that mirror Thl 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-% and the intedeukin/receptor signaling molecules IL-12/ IL-12R that are indispensable for ILC1 differentiation, in the helper ILCs of CHB patients. The elevated level of 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 ILCl-related factors. Furthermore, the activity of the ILC2s did not correlate with either HBV copies or liver damage. The findings in this study suggest potential proinflammatory roles for ILCls in CHB pathogenesis, potentiating these cells and their related molecules as targets of diagnostic, prognostic and/or therapeutic strategies for hepatitis B.