- 作者：Laurence Amiot ; Nicolas Vu ; Michel Rauch ; Annie L鈥橦elgoualc鈥檋 ; Fr茅d茅ric Chalmel ; Hugues Gascan ; Bruno Turlin ; Dominique Guyader ; Michel Samson
- 关键词：HCV ; hepatitis C virus ; TGF-尾 ; transforming growth factor 尾 ; IL ; interleukin ; ILT ; Immunoglobulin-like transcript receptors ; HIV ; human immunodeficiency virus ; HCMV ; human cytomegalovirus ; HBV ; hepatitis B virus ; IFN ; interferon ; OSM ; oncostatin ; MC ; mast cell ; HSC ; hepatic stellate cell ; SCF ; stem cell factor ; HCC ; hepatocellular carcinoma
- 刊名：Journal of Hepatology
- 出版年：February, 2014
- 年：2014
- 卷：60
- 期：2
- 页码：245-252
- 全文大小：2250 K
Background & Aims
Infection with hepatitis C virus is a worldwide health problem. An inadequate Th2 cytokine response promotes the fibrosis-cirrhosis fate. Immune-modulating molecules favoring a Th2 profile, such as HLA-G molecules of the HLA class Ib family, may play a role in chronic hepatitis. HLA-G contributes to the escape of tumors, and their involvement in viral infections has been increasingly described. The aim of this work was to study the expression of HLA-G in the liver, its cellular source and its regulation in cases of chronic C hepatitis.Methods
HLA-G cells in blocks of liver derived from patients infected with HCV were labeled by immunohistochemistry and enumerated. Double immunofluorescence allowed the identification of the cellular source. HLA-G secretion by a human mast cell line was quantified by ELISA after various stimulations. After treatment with IFN-伪, real-time PCR was performed to determine the kinetics of cytokine expression profiles, followed by heat map clustering analysis.
Results
The number of HLA-G+ cells was significantly associated with the area of fibrosis. For the first time, we identify the HLA-G+ cells as being mast cells. HLA-G secretion was significantly induced in human mast cells stimulated by IL-10 or interferons of class I. The transcriptome of the secretome of this cell line stimulated by IFN-伪 revealed that (i) the HLA-G gene is upregulated late, and that (ii) T lymphocytes and NK cells are recruited.
Conclusions
These findings suggest an autocrine loop in the genesis of HCV liver fibrosis, based on mast cells expressing HLA-G.