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Progression of fibrosis in patients with chronic viral hepatitis is associated with IL-17+ neutrophils
Zuzana Macek Jilkova1,2,†, Samia Afzal1,3,†, Hélène Marche1,2, Thomas Decaens1,2,4, Nathalie Sturm1,2,5, Evelyne Jouvin-Marche1,2, Bertrand Huard1,2 andPatrice N Marche1,2,*
DOI: 10.1111/liv.13060
This article is protected by copyright. All rights reserved.
Issue
Cover image for Vol. 36 Issue 1
Liver International
Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)
Article has an altmetric score of 2
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Author Information
Publication History
Author Information
1 Univ. Grenoble Alpes, IAB, Grenoble, France
2 INSERM U823, Grenoble, France
3 National Center of Excellence in Molecular Biology, University of The Punjab, Lahore, Pakistan
4 CHU-Grenoble Département d'Hépato-Gastro-Entérologie, La Tronche
5 CHU-Grenoble Département d'Anatomie et de Cytologie Pathologiques, La Tronche
† ZMJ and SA contributed equally to this work
* Correspondence: Patrice N Marche, Immunologie Analytique des Pathologies Chroniques, Institut Albert Bonniot, Centre de Recherche INSERM-UJF-U823, 38700 La Tronche,
Mail: [email protected], Phone: +33(0)476549495, Fax: +33(0)476549413.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.13060
Keywords:
Liver;Fibrosis;Neutrophils;IL-17
Abstract
Background & Aims
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 characterised in patients with liver fibrosis.
Methods
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.
Results
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.
Conclusions
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.
This article is protected by copyright. All rights reserved.
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发表于 2016-1-15 14:27
