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
滤泡辅助性T(follicular helper T,Tfh)细胞是近年新发现的受B细胞淋巴瘤6蛋白(Bcl-6)控制的一类独立CD4+T淋巴细胞亚群,以高表达趋化因子受体5(C-X-chemokine receptor type 5,CXCR5)、诱导性共刺激分子(inducible co-stimulator,ICOS...滤泡辅助性T(follicular helper T,Tfh)细胞是近年新发现的受B细胞淋巴瘤6蛋白(Bcl-6)控制的一类独立CD4+T淋巴细胞亚群,以高表达趋化因子受体5(C-X-chemokine receptor type 5,CXCR5)、诱导性共刺激分子(inducible co-stimulator,ICOS)、程序性细胞死亡蛋白-1(programmed cell death protein 1,PD-1)及白细胞介素(IL)-21为特征。Tfh的功能是辅助B淋巴细胞在生发中心淋巴滤泡内活化、增殖、分化成为浆细胞,产生高亲和力免疫球蛋白,促进Ig亚群类别转换及记忆B细胞形成。既往研究证明,Tfh功能异常与免疫缺陷病、过敏、肿瘤、器官移植排斥反应及心脏病等密切相关。近年来研究发现Tfh在自身免疫疾病的发病机制中扮演了重要角色。本文总结了Tfh的来源、分化、转录调控,并对Tfh与系统性红斑狼疮、类风湿关节炎、原发性干燥综合征及1型糖尿病等自身免疫疾病的关系进行综述。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.
文摘滤泡辅助性T(follicular helper T,Tfh)细胞是近年新发现的受B细胞淋巴瘤6蛋白(Bcl-6)控制的一类独立CD4+T淋巴细胞亚群,以高表达趋化因子受体5(C-X-chemokine receptor type 5,CXCR5)、诱导性共刺激分子(inducible co-stimulator,ICOS)、程序性细胞死亡蛋白-1(programmed cell death protein 1,PD-1)及白细胞介素(IL)-21为特征。Tfh的功能是辅助B淋巴细胞在生发中心淋巴滤泡内活化、增殖、分化成为浆细胞,产生高亲和力免疫球蛋白,促进Ig亚群类别转换及记忆B细胞形成。既往研究证明,Tfh功能异常与免疫缺陷病、过敏、肿瘤、器官移植排斥反应及心脏病等密切相关。近年来研究发现Tfh在自身免疫疾病的发病机制中扮演了重要角色。本文总结了Tfh的来源、分化、转录调控,并对Tfh与系统性红斑狼疮、类风湿关节炎、原发性干燥综合征及1型糖尿病等自身免疫疾病的关系进行综述。
