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, Patrice N Marche1,2. 1. IAB, University Grenoble Alpes, 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, France. 5. CHU-Grenoble Département d'Anatomie et de Cytologie Pathologiques, La Tronche, France.
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.
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.
Authors: John E Lewis; Steven E Atlas; Oscar L Higuera; Andrea Fiallo; Ammar Rasul; Ashar Farooqi; Olga Kromo; Laura A Lantigua; Eduard Tiozzo; Judi M Woolger; Sharon Goldberg; Armando Mendez; Allan E Rodriguez; Janet Konefal Journal: Evid Based Complement Alternat Med Date: 2018-05-03 Impact factor: 2.629
Authors: Zuzana Macek Jilkova; Ayca Zeybek Kuyucu; Keerthi Kurma; Séyédéh Tayébéh Ahmad Pour; Gaël S Roth; Giovanni Abbadessa; Yi Yu; Brian Schwartz; Nathalie Sturm; Patrice N Marche; Pierre Hainaut; Thomas Decaens Journal: Oncotarget Date: 2018-01-23