AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was adminis...AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.展开更多
目的:探讨外周血循环滤泡辅助性T细胞(Follicular helper T cells,Tfh)及相关细胞因子IL-21在银屑病患者中的表达水平及其与疾病活动度的关系。方法:收集38例银屑病患者及32例健康对照者,流式细胞术检测外周血循环CD4^+CXCR5^+Tfh和CD4^...目的:探讨外周血循环滤泡辅助性T细胞(Follicular helper T cells,Tfh)及相关细胞因子IL-21在银屑病患者中的表达水平及其与疾病活动度的关系。方法:收集38例银屑病患者及32例健康对照者,流式细胞术检测外周血循环CD4^+CXCR5^+Tfh和CD4^+CXCR5^+ICOS^+Tfh细胞比例以及Th17细胞比例;ELISA检测血清IL-21浓度;分析这些指标间及与银屑病疾病活动度评分PASI间的相关性。结果:与健康对照者相比,银屑病患者外周血循环CD4^+CXCR5^+Tfh和CD4^+CXCR5^+ICOS^+Tfh细胞比例更高,血清IL-21浓度和Th17细胞比例亦显著高于对照组(P<0.05);IL-21浓度与CD4^+CXCR5^+Tfh和CD4^+CXCR5^+ICOS^+Tfh细胞比例均显著正相关,而与Th17细胞比例间无显著相关性(P>0.05);且CD4^+CXCR5^+ICOS^+Tfh细胞比例和血清IL-21与银屑病疾病活动度PASI评分显著正相关,而CD4^+CXCR5^+Tfh则与之无显著相关性(P>0.05)。结论:银屑病患者外周血循环Tfh比例、IL-21浓度上调与银屑病患者疾病活动度密切相关,提示Tfh可能参与银屑病的发生发展过程,这一效应可能是通过分泌高水平IL-21实现;IL-21浓度与Tfh细胞比例相关,而与Th17细胞比例无相关性提示银屑病患者IL-21可能主要由Tfh细胞分泌。展开更多
基金Supported by National Natural Science Foundation of China,No.81260083Grants from the Guangxi Natural Science Foundation of China,No.2014jj AA40237
文摘AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.
文摘目的:探讨外周血循环滤泡辅助性T细胞(Follicular helper T cells,Tfh)及相关细胞因子IL-21在银屑病患者中的表达水平及其与疾病活动度的关系。方法:收集38例银屑病患者及32例健康对照者,流式细胞术检测外周血循环CD4^+CXCR5^+Tfh和CD4^+CXCR5^+ICOS^+Tfh细胞比例以及Th17细胞比例;ELISA检测血清IL-21浓度;分析这些指标间及与银屑病疾病活动度评分PASI间的相关性。结果:与健康对照者相比,银屑病患者外周血循环CD4^+CXCR5^+Tfh和CD4^+CXCR5^+ICOS^+Tfh细胞比例更高,血清IL-21浓度和Th17细胞比例亦显著高于对照组(P<0.05);IL-21浓度与CD4^+CXCR5^+Tfh和CD4^+CXCR5^+ICOS^+Tfh细胞比例均显著正相关,而与Th17细胞比例间无显著相关性(P>0.05);且CD4^+CXCR5^+ICOS^+Tfh细胞比例和血清IL-21与银屑病疾病活动度PASI评分显著正相关,而CD4^+CXCR5^+Tfh则与之无显著相关性(P>0.05)。结论:银屑病患者外周血循环Tfh比例、IL-21浓度上调与银屑病患者疾病活动度密切相关,提示Tfh可能参与银屑病的发生发展过程,这一效应可能是通过分泌高水平IL-21实现;IL-21浓度与Tfh细胞比例相关,而与Th17细胞比例无相关性提示银屑病患者IL-21可能主要由Tfh细胞分泌。
