慢性乙肝患者肝内IL-23/IL-17信号途径与Treg细胞之间的相互作用

Association of IL-23/17 pathway and regulatory T cells in chronic hepatitis B patients

目的探讨慢性乙肝患者体内FOXP3蛋白与炎症因子IL-23/IL-17信号途径之间的相互关系。方法采用qPCR、流式细胞术分析了39例慢性乙肝急性发作(ACLF)、56例慢性乙肝(CHB)及32例健康对照(HC)肝组织及外周血中的FOXP3及IL-23/IL-17信号途径相关炎症因子的表达,免疫组化及荧光共聚焦检测FOXP3在肝组织内的表达,定量PCR检测血清HBV DNA水平,酶联免疫吸附试验检测HBsAg浓度,全自动生化仪检测血清谷丙转氨酶(ALT)水平。结果 CHB患者外周血及肝组织内FOXP3 mRNA表达明显升高,肝内的FOXP3表达水平与患者血液中的HBV DNA水平及乙肝表面抗原(HB-sAg)浓度明显呈正相关。与健康对照组相比,慢性乙肝患者肝脏内的IL-23/IL-17信号通路相关的促炎因子也明显升高,且与FOXP3的表达水平升高呈正相关。结论 HBV感染的肝脏内IL-23/IL-17信号通路的活化并没有有效地被宿主的免疫机制如Treg细胞所抑制。因此,IL-23/IL-17信号通路可能是维持HBV病毒持续性感染的一个机制。

It has been shown that Th17 and Treg cells play important roles in chronic hepatitis B（CHB） pathogenesis,respectively.However,the relationship between the two cell types has not been clarified to date.To this end,we analyzed the expression patterns of FOXP3（Treg）-and IL-23/IL-17（Th17） pathway-related proinflammatory cytokines in 39 patients with acute-on-chronic liver failure,56 patients with CHB and 32 healthy controls.Results showed that FOXP3 expression was elevated in the CD4＋ T cell of peripheral blood mononuclear cells and liver tissues of patients with hepatitis B.The intrahepatic expression of FOXP3 strongly correlated with the copies of HBV DNA and the concentration of HBsAg.IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients＇ liver tissues,as compared to healthy controls.Moreover,FOXP3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients.The closely-correlated increase of FOXP3 and IL-23/IL-17 pathway activity in HBV-infected livers suggests that the proinflammatory IL-23/IL-17 pathway had not been effectively suppressed by the host immune machinery,such as Treg cells.Constitutive activation of the IL-23/17 pathway,thus,may support the chronic hepatitis B state.