Progression of fibrosis in patients with chronic viral hepatitis is associated with IL ‐17 + neutrophils
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 characterized 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.
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IL-13 may promote fibrosis independently of TGF-β, in part by directly targeting stromal and parenchymal cells, including epithelial populations and collagen-producing myofibroblasts.
“it may promote fibrosis independently of TGF-β134 in part by directly targeting stromal and parenchymal cells, including epithelial populations and collagen-producing myofibroblasts135”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [134]
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Fibrosis: from mechanisms to medicines
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Type 3 cytokines IL-17A and IL-22 drive TGF-β–dependent liver fibrosis
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- Authors
- Macek Jilkova, Z., Afzal, S., Marche, H., Decaens, T., Sturm, N., Jouvin‐Marche, E., Huard, B., & Marche, P. N.
- Affiliations
- IAB University Grenoble Alpes Grenoble France
- University of the Punjab (PK)
- Inserm (FR)
- Corresponding author
- Marche, Patrice N.
- Venue
- Liver International
- Publisher
- Wiley
- Published
- 2016-02-03
- Volume
- 36
- Issue
- 8
- Pages
- 1116-1124
- ISSN
- 0106-9543 (ISSN-L)
- 1478-3223
- 1478-3231
- OpenAlex
- W2228374045
- Cited by
- 40
- References
- 30
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 3
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Agence Nationale de Recherches sur le Sida et les Hepatites Virales
- Ligue Contre le Cancer (CD38, CD73)
- Fondation Innovations en Infectiologie
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- IL-17, neutrophils, liver fibrosis, chronic viral hepatitis, fibrosis progression, portal area, NKT cells, natural killer cells, macrophages
- MeSH terms
- Aged, Biopsy, Female, Fluorescent Antibody Technique, France, Hepatitis, Viral, Human, Humans, Liver Cirrhosis, Macrophages, Male, Middle Aged, Neutrophils, Disease Progression, Interleukin-17, Th17 Cells
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