title: Progression of fibrosis in patients with chronic viral hepatitis is associated with IL-17(+) neutrophils.
abstract: The pro-inflammatory cytokine IL-17 plays a crucial role in liver diseases associated with hepatic fibrosis and increased risk of cancer development. Nevertheless, the cellular source of this cytokine has never been characterized in patients with liver fibrosis.
  
  
  
  In this study, we investigated liver biopsies from 49 patients with chronic viral hepatitis at different stages of liver fibrosis. We monitored IL-17 production by intracellular flow cytometry, immunofluorescence and immunohistochemical in situ stainings, allowing a precise quantification, characterization and localization of IL-17(+) cells.
  
  
  
  Density of IL-17(+) cells increased with the stage of liver fibrosis specifically in fibrotic septa and portal areas (correlation coefficient r = 0.7373; P < 0.0001). Data clearly show that the frequency of intrahepatic IL-17(+) lymphocytes (including T, NKT and NK cells) was independent on stage of liver fibrosis, and we observed no statistical differences in number of IL-17(+) macrophages during progression of fibrosis. On the other hand, the number of IL-17(+) neutrophils in fibrotic septa and portal areas strongly correlated with the stages of fibrosis (correlation coefficient r = 0.6986; P < 0.0001), contributing significantly to total IL-17 production in liver tissue.
  
  
  
  Our data indicate that neutrophils represent an important source of IL-17 in the human liver, especially in late fibrosis stages. Inhibition of this specific harmful subset of neutrophils may offer therapeutic opportunities in fibrotic liver.
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|INSERM U823, Grenoble, France.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Macek Jilkova
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Samia
authors.initials: S
authors.lastname: Afzal
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|INSERM U823, Grenoble, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Marche
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|INSERM U823, Grenoble, France.|CHU-Grenoble Département d'Hépato-Gastro-Entérologie, La Tronche, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decaens
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|INSERM U823, Grenoble, France.|CHU-Grenoble Département d'Anatomie et de Cytologie Pathologiques, La Tronche, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sturm
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|INSERM U823, Grenoble, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jouvin-Marche
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|INSERM U823, Grenoble, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Huard
authors.affiliation: IAB, University Grenoble Alpes, Grenoble, France.|INSERM U823, Grenoble, France.
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
mesh_terms: D000368:Aged; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D005602:France; D006525:Hepatitis, Viral, Human / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology
chemical_list: D020381:Interleukin-17
keywords: IL-17; fibrosis; liver; neutrophils