IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells

• Published in: Gut Vol. 64; no. 9; pp. 1466 - 75
• Main Authors: Miot, Charline, Beaumont, Elodie, Duluc, Dorothée, Le Guillou-Guillemette, Hélène, Preisser, Laurence, Garo, Erwan, Blanchard, Simon, Hubert Fouchard, Isabelle, Créminon, Christophe, Lamourette, Patricia, Fremaux, Isabelle, Calès, Paul, Lunel-Fabiani, Françoise, Boursier, Jérôme, Braum, Oliver, Fickenscher, Helmut, Roingeard, Philippe, Delneste, Yves, Jeannin, Pascale
• Format: Journal Article
• Language: English
• Published: England Wiley-Blackwell 01-09-2015
• Subjects: Antiviral Agents - therapeutic use; Biomarkers - blood; Biopsy, Needle; Cancer; CD56 Antigen - immunology; CD56 Antigen - metabolism; Cells, Cultured - drug effects; Cells, Cultured - immunology; Cytokines - metabolism; Female; Hepatitis C, Chronic - blood; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Humans; Immunohistochemistry; Interferon-alpha - therapeutic use; Interleukins - blood; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Life Sciences; Male; Receptors, IgG - immunology; Receptors, IgG - metabolism; Severity of Illness Index; Statistics, Nonparametric; TNF-Related Apoptosis-Inducing Ligand - metabolism; INTERLEUKINS; HCV; IMMUNOLOGY IN HEPATOLOGY; INFLAMMATION
• ISSN: 0270-9139; 1468-3288; 1527-3350
• DOI: 10.1136/gutjnl-2013-306604

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.
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.
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.
This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection.