Expression of HLA-G by mast cells is associated with hepatitis C virus-induced liver fibrosis.

Laurence Amiot (1) , Nicolas Vu (1) , Michel Rauch (1) , Annie L' Helgoualc'H (1) , Frédéric Chalmel (2) , Hugues Gascan (3) , Bruno Turlin (4) , Dominique Guyader (5) , Michel Samson (1)

1 Irset - Institut de recherche en santé, environnement et travail
2 Transcriptional networks in gametogenesis and cancer
3 IGDR - Institut de Génétique et Développement de Rennes
4 Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes]
5 Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes]

BACKGROUND AND AIMS: Infection by 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, 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.

Mots clés: Hepatitis C; HCV; Liver; Fibrosis; HLA-G; Mast cell; IFN-α

Domaines: Maladies infectieuses

Laurence Amiot, Nicolas Vu, Michel Rauch, Annie L' Helgoualc'H, Frédéric Chalmel, et al.. Expression of HLA-G by mast cells is associated with hepatitis C virus-induced liver fibrosis.. Journal of Hepatology, 2013, 60 (2), pp.245-252. ⟨10.1016/j.jhep.2013.09.006⟩. ⟨hal-00874106⟩