title: Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice.
abstract: OBJECTIVE
  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)-β and α-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-β and α-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%, and 2.60% ± 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 of α-SMA, both in a dose-dependent manner, compared with the control group.
  
  
  CONCLUSIONS
  Th17/Treg imbalance exists in mice with liver fibrosis, which potentially promotes liver fibrosis via HSC activation.
authors.affiliation: Xiao-Fei Sun, Lei Gu, Wen-Sheng Deng, Qing Xu, Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Sun
authors.affiliation: Xiao-Fei Sun, Lei Gu, Wen-Sheng Deng, Qing Xu, Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gu
authors.affiliation: Xiao-Fei Sun, Lei Gu, Wen-Sheng Deng, Qing Xu, Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Deng
authors.affiliation: Xiao-Fei Sun, Lei Gu, Wen-Sheng Deng, Qing Xu, Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D005434:Flow Cytometry; D055166:Hepatic Stellate Cells / Q000166:cytology; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride
keywords: Carbon tetrachloride; Hepatic fibrosis; Hepatic stellate cell; T helper 17 cell; Treg cell