title: Expression of HLA-G by mast cells is associated with hepatitis C virus-induced liver fibrosis.
abstract: OBJECTIVE
  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-α, 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-α 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement & Travail (IRSET), F-35043 Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France; Department of Biology, University Hospital Pontchaillou, CHU Pontchaillou, Rennes, France. Electronic address: laurence.amiot@univ-rennes1.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Amiot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement & Travail (IRSET), F-35043 Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement & Travail (IRSET), F-35043 Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Rauch
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement & Travail (IRSET), F-35043 Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France.
authors.forename: Annie
authors.initials: A
authors.lastname: L'Helgoualc'h
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement & Travail (IRSET), F-35043 Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chalmel
authors.affiliation: CNRS, UMR 6290, Institute of Genetics and Development of Rennes, Rennes, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Gascan
authors.affiliation: Université de Rennes 1, F-35043 Rennes, France; Department of Pathology, University Hospital Pontchaillou, CHU Pontchaillou, Rennes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Turlin
authors.affiliation: Université de Rennes 1, F-35043 Rennes, France; Department of Hepatology, University Hospital Pontchaillou, CHU Pontchaillou, Rennes, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guyader
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement & Travail (IRSET), F-35043 Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D059951:HLA-G Antigens; D016898:Interferon-alpha
keywords: Fibrosis; HBV; HCC; HCMV; HCV; HIV; HLA-G; HSC; Hepatitis C; IFN; IFN-α; IL; ILT; Immunoglobulin-like transcript receptors; Liver; MC; Mast cell; OSM; SCF; TGF-β; hepatic stellate cell; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; human cytomegalovirus; human immunodeficiency virus; interferon; interleukin; mast cell; oncostatin; stem cell factor; transforming growth factor β