title: IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells.
abstract: OBJECTIVE
  Interleukin-26 (IL-26) is a member of the IL-10 cytokine family, first discovered based on its peculiar expression by virus-transformed T cells. IL-26 is overexpressed in chronic inflammation (rheumatoid arthritis and Crohn's disease) and induces proinflammatory cytokines by myeloid cells and some epithelial cells. We thus investigated the expression and potential role of IL-26 in chronic HCV infection, a pathology associated with chronic inflammation.
  
  
  METHODS
  IL-26 was quantified in a cohort of chronically HCV-infected patients, naive of treatment and its expression in the liver biopsies investigated by immunohistochemistry. We also analysed the ability of IL-26 to modulate the activity of natural killer (NK) cells, which control HCV infection.
  
  
  RESULTS
  The serum levels of IL-26 are enhanced in chronically HCV-infected patients, mainly in those with severe liver inflammation. Immunohistochemistry reveals an intense IL-26 staining in liver lesions, mainly in infiltrating CD3+ cells. We also show that NK cells from healthy subjects and from HCV-infected patients are sensitive to IL-26. IL-26 upregulates membrane tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on CD16- CD56(bright) NK cells, enabling them to kill HCV-infected hepatoma cells, with the same efficacy as interferon (IFN)-α-treated NK cells. IL-26 also induces the expression of the antiviral cytokines IFN-β and IFN-γ, and of the proinflammatory cytokines IL-1β and TNF-α by NK cells.
  
  
  CONCLUSIONS
  This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection.
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France Laboratoire d'Immunologie et Allergologie, CHU Angers, Angers, France.
authors.forename: Charline
authors.initials: C
authors.lastname: Miot
authors.affiliation: Université de Tours, Tours, France Inserm, Unité 966, Tours, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Beaumont
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Duluc
authors.affiliation: Laboratoire de Bactériologie-Virologie, CHU Angers, Angers, France Université d'Angers, UPRES 3859, Angers, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Le Guillou-Guillemette
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Preisser
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Garo
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France Laboratoire d'Immunologie et Allergologie, CHU Angers, Angers, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Blanchard
authors.affiliation: Service d'Hépato-Gastroentérologie, CHU Angers, Angers, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hubert Fouchard
authors.affiliation: Service de Pharmacologie et d'Immunoanalyse, Commissariat à l'Energie Atomique Saclay, iBiTec-S, Gif sur Yvette, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Créminon
authors.affiliation: Service de Pharmacologie et d'Immunoanalyse, Commissariat à l'Energie Atomique Saclay, iBiTec-S, Gif sur Yvette, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lamourette
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fremaux
authors.affiliation: Université d'Angers, UPRES 3859, Angers, France Service d'Hépato-Gastroentérologie, CHU Angers, Angers, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.affiliation: Laboratoire de Bactériologie-Virologie, CHU Angers, Angers, France Université d'Angers, UPRES 3859, Angers, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Lunel-Fabiani
authors.affiliation: Service d'Hépato-Gastroentérologie, CHU Angers, Angers, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boursier
authors.affiliation: Institute for Infection Medicine, Christian Albrecht University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Braum
authors.affiliation: Institute for Infection Medicine, Christian Albrecht University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Fickenscher
authors.affiliation: Université de Tours, Tours, France Inserm, Unité 966, Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Roingeard
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France Laboratoire d'Immunologie et Allergologie, CHU Angers, Angers, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.affiliation: Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France Laboratoire d'Immunologie et Allergologie, CHU Angers, Angers, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001707:Biopsy, Needle; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000627:therapeutic use*; D007378:Interleukins / Q000097:blood*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D019002:CD56 Antigen; D016207:Cytokines; C406767:IL26 protein, human; D016898:Interferon-alpha; D007378:Interleukins; D017452:Receptors, IgG; D053221:TNF-Related Apoptosis-Inducing Ligand
keywords: HCV; IMMUNOLOGY IN HEPATOLOGY; INFLAMMATION; INTERLEUKINS