Sun XF, Gu L, Deng WS, Xu Q. Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice.
World J Gastroenterol 2014;
20:2062-2070. [PMID:
24616573 PMCID:
PMC3934476 DOI:
10.3748/wjg.v20.i8.2062]
[Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Revised: 11/01/2013] [Accepted: 11/19/2013] [Indexed: 02/06/2023] Open
Abstract
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)-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.
CONCLUSION: Th17/Treg imbalance exists in mice with liver fibrosis, which potentially promotes liver fibrosis via HSC activation.
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