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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Translational Medicine 1/2017

Levels of hepatic Th17 cells and regulatory T cells upregulated by hepatic stellate cells in advanced HBV-related liver fibrosis

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2017
Autoren:
Xiaoyan Li, Yujie Su, Xuefeng Hua, Chan Xie, Jing Liu, Yuehua Huang, Liang Zhou, Min Zhang, Xu Li, Zhiliang Gao
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12967-017-1167-y) contains supplementary material, which is available to authorized users.
Xiaoyan Li and Yujie Su contributed equally to this work

Abstract

Background

Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive.

Methods

Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University. Liver tissues at least 3 cm away from the tumor site were used for the analyses. Levels of Th17 cells and regulatory T cells were detected by flow cytometry analysis and immunohistochemistry. In vitro experiment, we adopted magnetic cell sorting to investigate how hepatic stellate cells regulate the levels of Th17 cells and regulatory T cells.

Results

We found that hepatic Th17 cells and regulatory T cells were increased in patients with advanced stage HBV-related liver fibrosis. Hepatic stellate cells upregulated the levels of Th17 cells and regulatory T cells via PGE2/EP2 and EP4 pathway.

Conclusions

We found that the increased levels of Th17 cells and regulatory T cells were upregulated by hepatic stellate cells. These results may provide insight into the role of hepatic stellate cells and Th17 cells and regulatory T cells in the persistence of fibrosis and into the occurrence of hepatocellular carcinoma following cirrhosis.
Zusatzmaterial
Additional file 1. Additional material.
Additional file 2: Figure S1. Expression of ki67 on Th17 cells and Tregs regulated by HSC. (A, C) the expression of ki67 on Th17 cells (A) and Tregs (C) regulated by LX-2 cell lines. (B, D) the expression of ki67 on Th17 cells (B) and Tregs (D) regulated by pHSC. Both LX-2 and pHSC did not affect significantly the expression of ki67 on Th17 cells and Tregs.
Additional file 3: Figure S2. The expression of EP2 and EP4.Flow cytometry analysis of the expression of EP2 and EP4 in freshly isolated CD4+ T cells from peripheral blood and liver tissues. The histogram indicates that both circulating and intrahepatic CD4+ T cells express EP2 and EP4 receptors (black line: isotype, grey line: EP2 or EP4). The data shown are representative histograms of at least 10 individuals from more than three independent experiments.
Additional file 4: Figure S3. Concentration of serum PGE2 of patients. Statistic analysis of the concentration of serum PGE2 in Group 2 (black filled profiles) compared with Group 1 (open profiles) by ELISA. *: p < 0.05, **: p < 0.01, ***: p < 0.001.
Literatur
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