title: IFN-λ-mediated IL-12 production in macrophages induces IFN-γ production in human NK cells.
abstract: With increasing interest in alternative options to interferon-alpha-based treatments, IFN-λ has shown therapeutic promise in a variety of diseases. Although the antiviral activity of IFN-λ has been extensively studied, there is limited knowledge regarding the immunological functions of IFN-λ and how these differ from those of other classes of IFNs. In this study, we investigated the effects of IFN-λ on primary human NK cells, both in a direct and indirect capacity. We demonstrate that in contrast to interferon-alpha, IFN-λ is unable to directly stimulate NK cells, due to the absence of IFN-λ receptor chain 1 (IFN-λR1) on NK cells. However, IFN-λ, in combination with TLR4 challenge, is able to induce the production of select members of the IL-12 family of cytokines in monocyte-derived macrophages. We further show that through macrophage-mediated IL-12 production, IFN-λ is able to indirectly affect NK cells and ultimately induce IFN-γ production.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Rik A
authors.initials: RA
authors.lastname: de Groen
authors.forename: Arjan
authors.initials: A
authors.lastname: Boltjes
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Bi-Sheng
authors.initials: BS
authors.lastname: Liu
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.forename: Jacques
authors.initials: J
authors.lastname: Friborg
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D002450:Cell Communication / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007372:Interferons; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D061251:Primary Cell Culture; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007371:Interferon-gamma; D007372:Interferons; D018664:Interleukin-12; D007378:Interleukins; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C495345:TLR4 protein, human
keywords: Hepatitis C; IFN-γ; IL-29; Innate immunity; Macrophages; NK cells