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- Title
Progression of fibrosis in patients with chronic viral hepatitis is associated with IL-17<sup>+</sup> neutrophils.
- Authors
Macek Jilkova, Zuzana; Afzal, Samia; Marche, Hélène; Decaens, Thomas; Sturm, Nathalie; Jouvin ‐ Marche, Evelyne; Huard, Bertrand; Marche, Patrice N.
- 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.
- Subjects
FIBROSIS; VIRAL hepatitis; INTERLEUKIN-17; PHYSIOLOGICAL effects of cytokines; IMMUNOFLUORESCENCE; PATIENTS; DISEASE risk factors
- Publication
Liver International, 2016, Vol 36, Issue 8, p1116
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.13060