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:系统评价外周血辅助性T细胞22(Th22细胞)比例与肿瘤的相关性。方法:计算机检索PubMed、EMBASE、Web of Science、CNKI及Wanfang等数据库,搜集建库至2018年11月25日公开发表的关于外周血Th22细胞比例与肿瘤发生发展相关性的研究。采...目的:系统评价外周血辅助性T细胞22(Th22细胞)比例与肿瘤的相关性。方法:计算机检索PubMed、EMBASE、Web of Science、CNKI及Wanfang等数据库,搜集建库至2018年11月25日公开发表的关于外周血Th22细胞比例与肿瘤发生发展相关性的研究。采用RevMan5.3软件进行Meta分析。结果:最终共纳入26个研究,包括8种肿瘤,共计1020例患者和679例健康对照。Meta分析的结果显示,肿瘤组外周血Th22细胞比例高于健康人群组[WMD=1.37,95%CI(1.07,1.68),P<0.00001],并且晚期患者外周血Th22细胞比例高于早期患者[WMD=0.41,95%CI(0.17,0.66),P=0.0009]。亚组分析结果显示,在不同肿瘤类型(除脑胶质瘤外)、不同肿瘤分期、不同Th22细胞圈定方法以及不同NOS评分的研究中,患者的外周血Th22细胞比例均比健康人群高(P均<0.05)。结论:外周血Th22细胞比例与肿瘤发生相关,Th22细胞比例升高可能会增加发生肿瘤的风险,且对肿瘤的恶性程度具有一定的提示作用。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:系统评价外周血辅助性T细胞22(Th22细胞)比例与肿瘤的相关性。方法:计算机检索PubMed、EMBASE、Web of Science、CNKI及Wanfang等数据库,搜集建库至2018年11月25日公开发表的关于外周血Th22细胞比例与肿瘤发生发展相关性的研究。采用RevMan5.3软件进行Meta分析。结果:最终共纳入26个研究,包括8种肿瘤,共计1020例患者和679例健康对照。Meta分析的结果显示,肿瘤组外周血Th22细胞比例高于健康人群组[WMD=1.37,95%CI(1.07,1.68),P<0.00001],并且晚期患者外周血Th22细胞比例高于早期患者[WMD=0.41,95%CI(0.17,0.66),P=0.0009]。亚组分析结果显示,在不同肿瘤类型(除脑胶质瘤外)、不同肿瘤分期、不同Th22细胞圈定方法以及不同NOS评分的研究中,患者的外周血Th22细胞比例均比健康人群高(P均<0.05)。结论:外周血Th22细胞比例与肿瘤发生相关,Th22细胞比例升高可能会增加发生肿瘤的风险,且对肿瘤的恶性程度具有一定的提示作用。