Imbalance between T helper type 17 and T regulatory cells in patients with primary biliary cirrhosis: the serum cytokine profile and peripheral cell population
Imbalance between T helper type 17 and T regulatory cells in patients with primary biliary cirrhosis: the serum cytokine profile and peripheral cell population
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DOI：
10.1111/j.1365-2249.2009.03898.x
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发表时间：
2009-05-01
影响因子：
4.6
通讯作者：
Zhong, R.
中科院分区：
文献类型：
--
作者：
Rong, G.;Zhou, Y.;Zhong, R.
原发性胆汁性肝硬化（PBC）是一种器官特异性自身免疫性肝病，其特征是肝内小胆管的进行性丢失。涉及T细胞反应的细胞免疫机制被认为在PBC的发病机制中起重要作用。最近的研究独立地揭示了在一些自身免疫性疾病中增强的T辅助细胞17型（Th 17）反应和减弱的T调节细胞（T-reg）反应，表明Th 17/T-reg失衡在自身免疫发病机制中的作用。这促使我们研究PBC患者外周血中Th 17/T-reg平衡是否被打破，如果是，什么细胞因子可能导致这种失衡。采用实时荧光定量聚合酶链反应（real-time quantitative polymerase chain reaction，RT-PCR）和酶联免疫吸附法（enzyme-linked immunosorbent assay，ELISA）分别检测36例PBC患者、28例慢性B型肝炎患者和28例健康对照者外周血中11个Th 17/T-reg分化相关基因的表达及相应细胞因子的浓度。通过流式细胞术分析外周Th 17和T-reg细胞。PBC患者外周血Th 17相关细胞因子水平明显升高。与细胞因子谱一致，Th 17细胞群和类维生素A相关孤儿受体γ t表达显著增加。而PBC患者外周血中T-reg细胞数和叉头盒P3表达明显降低。我们的研究表明，PBC患者存在Th 17/T-reg失衡，无论是细胞因子谱还是细胞数量，表明其在PBC免疫自身耐受的破坏中可能发挥作用。白细胞介素-23可能在Th 17相关的自身免疫中发挥重要作用。
Primary biliary cirrhosis (PBC) is an organ-specific autoimmune liver disease characterized by progressive loss of intrahepatic small bile ducts. Cellular immune mechanisms involving T cell reaction are thought to be involved significantly in the pathogenesis of PBC. Recent studies have independently revealed enhanced T helper type 17 (Th17) response and weakened T regulatory cell (T-reg) response in some autoimmune diseases, indicating a role of Th17/T-reg imbalance in the pathogenesis of autoimmunity. This prompted us to investigate whether the Th17/T-reg balance was broken in the peripheral blood of patients with PBC and, if it was, what cytokine circumstances might contribute to this imbalance. The expression of 11 Th17/T-reg differentiation-related genes and serum concentrations of the corresponding cytokines in 36 patients with PBC, 28 patients with chronic hepatitis B and 28 healthy controls were measured by real-time quantitative-polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Peripheral Th17 and T-reg cells were analysed by flow cytometry. Th17-related cytokines were increased significantly in patients with PBC. Consistent with the cytokine profile, the Th17 cell population and retinoid-related orphan receptor gamma t expression were increased markedly. In contrast, the T-reg cell population and forkhead box P3 expression were decreased dramatically in the peripheral blood of patients with PBC. Our study revealed that the Th17/T-reg imbalance, both cytokine profile and cell numbers, exists in patients with PBC, suggesting its potential role in the breakdown of immune self-tolerance in PBC. Interleukin-23, which characterized the imbalanced cytokine profile, may play an essential role in Th17-related human autoimmunity.