Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice

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)-beta and alpha-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-beta and alpha-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 alpha-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. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.