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1Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice显示文摘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.Xiao-Fei Sun Lei Gu Wen-Sheng Deng Qing Xu 2014World Journal of Gastroenterology2014,20,8:20
2Tolerance in liver transplantation: Biomarkers and clinical relevance显示文摘Transplantation is the optimal treatment for end-stage organ failure,and modern immunosuppression has allowed important progress in short-term outcomes. However,immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus,a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor Fox P3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise,other immune cells,such as dendritic cells,monocyte/macrophages or natural killer cells,have been described as part of the process known as 'operational tolerance'. However,translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way,a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multicenter clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.Alberto Baroja-Mazo Beatriz Revilla-Nuin Pascual Parrilla Laura Martínez-Alarcón Pablo Ramírez José Antonio Pons 2016World Journal of Gastroenterology2016,22,34:4
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