Charline Miot1, Elodie Beaumont2, Dorothée Duluc3, Hélène Le Guillou-Guillemette4, Laurence Preisser3, Erwan Garo3, Simon Blanchard1, Isabelle Hubert Fouchard5, Christophe Créminon6, Patricia Lamourette6, Isabelle Fremaux3, Paul Calès7, Françoise Lunel-Fabiani4, Jérôme Boursier5, Oliver Braum8, Helmut Fickenscher8, Philippe Roingeard2, Yves Delneste1, Pascale Jeannin1. 1. Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France Laboratoire d'Immunologie et Allergologie, CHU Angers, Angers, France. 2. Université de Tours, Tours, France Inserm, Unité 966, Tours, France. 3. Université d'Angers, Angers, France Inserm, Unité 892, Angers, France CNRS, Unité 6299, Angers, France. 4. Laboratoire de Bactériologie-Virologie, CHU Angers, Angers, France Université d'Angers, UPRES 3859, Angers, France. 5. Service d'Hépato-Gastroentérologie, CHU Angers, Angers, France. 6. Service de Pharmacologie et d'Immunoanalyse, Commissariat à l'Energie Atomique Saclay, iBiTec-S, Gif sur Yvette, France. 7. Université d'Angers, UPRES 3859, Angers, France Service d'Hépato-Gastroentérologie, CHU Angers, Angers, France. 8. Institute for Infection Medicine, Christian Albrecht University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Abstract
OBJECTIVE: Interleukin-26 (IL-26) is a member of the IL-10 cytokine family, first discovered based on its peculiar expression by virus-transformed T cells. IL-26 is overexpressed in chronic inflammation (rheumatoid arthritis and Crohn's disease) and induces proinflammatory cytokines by myeloid cells and some epithelial cells. We thus investigated the expression and potential role of IL-26 in chronic HCV infection, a pathology associated with chronic inflammation. DESIGN: IL-26 was quantified in a cohort of chronically HCV-infected patients, naive of treatment and its expression in the liver biopsies investigated by immunohistochemistry. We also analysed the ability of IL-26 to modulate the activity of natural killer (NK) cells, which control HCV infection. RESULTS: The serum levels of IL-26 are enhanced in chronically HCV-infected patients, mainly in those with severe liver inflammation. Immunohistochemistry reveals an intense IL-26 staining in liver lesions, mainly in infiltrating CD3+ cells. We also show that NK cells from healthy subjects and from HCV-infected patients are sensitive to IL-26. IL-26 upregulates membrane tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on CD16- CD56(bright) NK cells, enabling them to kill HCV-infected hepatoma cells, with the same efficacy as interferon (IFN)-α-treated NK cells. IL-26 also induces the expression of the antiviral cytokines IFN-β and IFN-γ, and of the proinflammatory cytokines IL-1β and TNF-α by NK cells. CONCLUSIONS: This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
OBJECTIVE:Interleukin-26 (IL-26) is a member of the IL-10 cytokine family, first discovered based on its peculiar expression by virus-transformed T cells. IL-26 is overexpressed in chronic inflammation (rheumatoid arthritis and Crohn's disease) and induces proinflammatory cytokines by myeloid cells and some epithelial cells. We thus investigated the expression and potential role of IL-26 in chronic HCV infection, a pathology associated with chronic inflammation. DESIGN:IL-26 was quantified in a cohort of chronically HCV-infectedpatients, naive of treatment and its expression in the liver biopsies investigated by immunohistochemistry. We also analysed the ability of IL-26 to modulate the activity of natural killer (NK) cells, which control HCV infection. RESULTS: The serum levels of IL-26 are enhanced in chronically HCV-infectedpatients, mainly in those with severe liver inflammation. Immunohistochemistry reveals an intense IL-26 staining in liver lesions, mainly in infiltrating CD3+ cells. We also show that NK cells from healthy subjects and from HCV-infectedpatients are sensitive to IL-26. IL-26 upregulates membrane tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on CD16- CD56(bright) NK cells, enabling them to kill HCV-infected hepatoma cells, with the same efficacy as interferon (IFN)-α-treated NK cells. IL-26 also induces the expression of the antiviral cytokines IFN-β and IFN-γ, and of the proinflammatory cytokines IL-1β and TNF-α by NK cells. CONCLUSIONS: This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Entities:
Keywords:
HCV; IMMUNOLOGY IN HEPATOLOGY; INFLAMMATION; INTERLEUKINS
Authors: Angeline Tilly Dang; Rosane Mb Teles; David I Weiss; Kislay Parvatiyar; Euzenir N Sarno; Maria T Ochoa; Genhong Cheng; Michel Gilliet; Barry R Bloom; Robert L Modlin Journal: J Clin Invest Date: 2019-04-02 Impact factor: 14.808