Polarized effector function of NK cells in chronic hepatitis C is partially dependent on the IL28B genotype

Abstract

Event Abstract Back to Event Polarized effector function of NK cells in chronic hepatitis C is partially dependent on the IL28B genotype Magdalena Rogalska-Taranta1, 2*, Antoaneta A. Markova1, Sandra Westhaus1, Sebastian Lunemann1, Andrzej Taranta1, Verena Schlaphoff1, Michael P. Manns1, Markus Cornberg1, Sandra Ciesek1 and Heiner Wedemeyer1 1 Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Germany 2 Medical University of Bialystok, Department of Infectious Diseases and Hepatology, Poland Background: IFNα-induced expression of TRAIL on NK cells correlates with HCV-RNA decline during interferon alpha-based therapy. A polymorphism close to the IL28B genotype has been identified to be the most important factor in determining treatment response. However, the role of the IL28B genotype in type-I-interferon-dependent regulation of NK cells function is unknown. Methods: NK cells from healthy controls and chronic hepatitis C (CHC) patients were studied in vitro after IFNα-stimulation. Upregulation of TRAIL, CD107a and intracellular cytokine production were investigated by flow-cytometry after co-cultering with K562 or Huh7.5 cells. NK cells were also co-cultured with Huh7.5 Luc-NS3-5B/JFH1 subgenomic replicon cells to assess antiviral effector functions. The IL28B SNP rs12979860 was determined by melting curve analysis. Results: NK cells of CHC patients showed a marked polarization towards cytotoxicity in response to IFNα-stimulation with significantly higher TRAIL upregulation but lower IFNγ and TNFα production. Co-cultering of HCV replicon cells with resting NK cells had modest antiviral effects while IFNα-stimulated NK cells significantly reduced HCV replication. Cytokine production but not TRAIL expression was higher in healthy subjects carrying the IL28B-CC allele. In contrast, CHC patients with an IL28B-CT or -TT genotype showed higher IFNγ expression. The percentage of IFNγ-positive NK cells after IFNα-stimulation correlated with ALT levels only in IL28B-TT-patients. Discussion: Higher cytokine production of NK cells in IL28B-CC healthy individuals may reflect better early effector functions supporting spontaneous HCV clearance in acute hepatitis-C. In contrast, the increased activity of NK cells in IL28B-TT CHC patients may contribute to the activity of liver disease. Keywords: NK cells, IL28B, TRAIL, IFNγ, IFNα, Hepatitis C Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Rogalska-Taranta M, Markova AA, Westhaus S, Lunemann S, Taranta A, Schlaphoff V, Manns MP, Cornberg M, Ciesek S and Wedemeyer H (2013). Polarized effector function of NK cells in chronic hepatitis C is partially dependent on the IL28B genotype. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01072 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Magdalena Rogalska-Taranta, Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany, m.rogalska.taranta@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Magdalena Rogalska-Taranta Antoaneta A Markova Sandra Westhaus Sebastian Lunemann Andrzej Taranta Verena Schlaphoff Michael P Manns Markus Cornberg Sandra Ciesek Heiner Wedemeyer Google Magdalena Rogalska-Taranta Antoaneta A Markova Sandra Westhaus Sebastian Lunemann Andrzej Taranta Verena Schlaphoff Michael P Manns Markus Cornberg Sandra Ciesek Heiner Wedemeyer Google Scholar Magdalena Rogalska-Taranta Antoaneta A Markova Sandra Westhaus Sebastian Lunemann Andrzej Taranta Verena Schlaphoff Michael P Manns Markus Cornberg Sandra Ciesek Heiner Wedemeyer PubMed Magdalena Rogalska-Taranta Antoaneta A Markova Sandra Westhaus Sebastian Lunemann Andrzej Taranta Verena Schlaphoff Michael P Manns Markus Cornberg Sandra Ciesek Heiner Wedemeyer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.