Objective:To investigate whether kynurenine/aryl hydrocarbon receptor(AHR)affects the maternal-fetal tolerance by involving the differentiation of T helper 17(Th17)/regulatory T(Treg)cells,and to provide theoretical b...Objective:To investigate whether kynurenine/aryl hydrocarbon receptor(AHR)affects the maternal-fetal tolerance by involving the differentiation of T helper 17(Th17)/regulatory T(Treg)cells,and to provide theoretical basic for new treatment of unexplained abortion.Methods:Flow cytometry(FCM)was used to detect the expression of AHR in peripheral/decidual CD4+T,Treg,and Th17 cells.The effect of Kyn on the differentiation of peripheral/decidual naïve T-cells under Treg-/Th17-polarizing condition was detected by FCM;enzyme-linked immunosorbent assay was performed to examine the level of Kyn in villus and decidual tissues from normal pregnancy(NP)and unexplained abortion(UA).Student’s t-test in the case of two groups or one-way ANOVA in multiple groups was used.Results:AHR expression in CD4+T-cells was decreased in decidua versus blood in early pregnancy(P<0.0001).Kyn could promote the differentiation of peripheral and decidual naïve T-cells to Th17 cells under Treg-polarizing conditions(P<0.01).There was no statistical significance about the concentration of Kyn in decidual or villi tissues between NP and UA,and compared with NP,the expression of AHR in decidual CD4+T-cells from UA was increased(P<0.001).Conclusions:Kyn/AHR promotes Th17 and restricts Treg cells’differentiation,which is involved in maintaining the balance of Treg/Th17 cells at the maternal-fetal interface.展开更多
AIM:To investigate the effect of T helper(Th)17/T regulatory(Treg)cells on hepatic fibrosis in mice and its possible mechanism.METHODS:Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride....AIM:To investigate the effect of T helper(Th)17/T regulatory(Treg)cells on hepatic fibrosis in mice and its possible mechanism.METHODS:Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride.Hepatic pathological changes were observed by hematoxylin and eosin staining;the protein levels of interleukin(IL)-6,transforming growth factor(TGF)-βandα-smooth muscle actin(SMA)in liver tissue were determined by Western blotting;and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry.In addition,hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells.Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation.RESULTS:In the model group,there were different degrees of fibroplasia,degeneration and necrosis.The protein levels of IL-6,TGF-βandα-SMA in liver tissue were significantly higher than those in the control group at 12 wk(P<0.05).Compared with the control group,the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually.Furthermore,at 4,8 and 12 wk,there were significant differences in the number of Th17 cells(0.52%±0.16%,1.46%±0.24%,and2.60%±0.41%,respectively,P<0.05)and Treg cells(2.99%±0.40%,2.16%±0.50%,and 1.49%±0.34%,respectively,P<0.05).In vitro,Th17 cells promoted,whereas Treg cells inhibited the expression ofα-SMA,both in a dose-dependent manner,compared with the control group.CONCLUSION:Th17/Treg imbalance exists in mice with liver fibrosis,which potentially promotes liver fibrosis via HSC activation.展开更多
基金supported by grants from the Natural Science Foundation of China(No.81373868).
文摘Objective:To investigate whether kynurenine/aryl hydrocarbon receptor(AHR)affects the maternal-fetal tolerance by involving the differentiation of T helper 17(Th17)/regulatory T(Treg)cells,and to provide theoretical basic for new treatment of unexplained abortion.Methods:Flow cytometry(FCM)was used to detect the expression of AHR in peripheral/decidual CD4+T,Treg,and Th17 cells.The effect of Kyn on the differentiation of peripheral/decidual naïve T-cells under Treg-/Th17-polarizing condition was detected by FCM;enzyme-linked immunosorbent assay was performed to examine the level of Kyn in villus and decidual tissues from normal pregnancy(NP)and unexplained abortion(UA).Student’s t-test in the case of two groups or one-way ANOVA in multiple groups was used.Results:AHR expression in CD4+T-cells was decreased in decidua versus blood in early pregnancy(P<0.0001).Kyn could promote the differentiation of peripheral and decidual naïve T-cells to Th17 cells under Treg-polarizing conditions(P<0.01).There was no statistical significance about the concentration of Kyn in decidual or villi tissues between NP and UA,and compared with NP,the expression of AHR in decidual CD4+T-cells from UA was increased(P<0.001).Conclusions:Kyn/AHR promotes Th17 and restricts Treg cells’differentiation,which is involved in maintaining the balance of Treg/Th17 cells at the maternal-fetal interface.
基金Supported by Grants for Scientific Research Innovation Project of Shanghai Education Committee,China,No.13yz040
文摘AIM:To investigate the effect of T helper(Th)17/T regulatory(Treg)cells on hepatic fibrosis in mice and its possible mechanism.METHODS:Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride.Hepatic pathological changes were observed by hematoxylin and eosin staining;the protein levels of interleukin(IL)-6,transforming growth factor(TGF)-βandα-smooth muscle actin(SMA)in liver tissue were determined by Western blotting;and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry.In addition,hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells.Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation.RESULTS:In the model group,there were different degrees of fibroplasia,degeneration and necrosis.The protein levels of IL-6,TGF-βandα-SMA in liver tissue were significantly higher than those in the control group at 12 wk(P<0.05).Compared with the control group,the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually.Furthermore,at 4,8 and 12 wk,there were significant differences in the number of Th17 cells(0.52%±0.16%,1.46%±0.24%,and2.60%±0.41%,respectively,P<0.05)and Treg cells(2.99%±0.40%,2.16%±0.50%,and 1.49%±0.34%,respectively,P<0.05).In vitro,Th17 cells promoted,whereas Treg cells inhibited the expression ofα-SMA,both in a dose-dependent manner,compared with the control group.CONCLUSION:Th17/Treg imbalance exists in mice with liver fibrosis,which potentially promotes liver fibrosis via HSC activation.
