PT - JOURNAL ARTICLE AU - Charline Miot AU - Elodie Beaumont AU - Dorothée Duluc AU - Hélène Le Guillou-Guillemette AU - Laurence Preisser AU - Erwan Garo AU - Simon Blanchard AU - Isabelle Hubert Fouchard AU - Christophe Créminon AU - Patricia Lamourette AU - Isabelle Fremaux AU - Paul Calès AU - Françoise Lunel-Fabiani AU - Jérôme Boursier AU - Oliver Braum AU - Helmut Fickenscher AU - Philippe Roingeard AU - Yves Delneste AU - Pascale Jeannin TI - IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells AID - 10.1136/gutjnl-2013-306604 DP - 2015 Sep 01 TA - Gut PG - 1466--1475 VI - 64 IP - 9 4099 - http://gut.bmj.com/content/64/9/1466.short 4100 - http://gut.bmj.com/content/64/9/1466.full SO - Gut2015 Sep 01; 64 AB - 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− CD56bright 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.