title: IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness.
abstract: IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their coculture, showing the importance of IL-27 during DC-NK-cell crosstalk. Accordingly, human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion, which was associated with an IL-27-driven upregulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK-cell-mediated cytotoxicity against Raji, T-47D, and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK-cell-mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent cell-mediated cytotoxicity against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations.
authors.affiliation: Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ziblat
authors.forename: Carolina I
authors.initials: CI
authors.lastname: Domaica
authors.forename: Raúl G
authors.initials: RG
authors.lastname: Spallanzani
authors.forename: Ximena L Raffo
authors.initials: XL
authors.lastname: Iraolagoitia
authors.forename: Lucas E
authors.initials: LE
authors.lastname: Rossi
authors.forename: Damián E
authors.initials: DE
authors.lastname: Avila
authors.forename: Nicolás I
authors.initials: NI
authors.lastname: Torres
authors.forename: Mercedes B
authors.initials: MB
authors.lastname: Fuertes
authors.forename: Norberto W
authors.initials: NW
authors.lastname: Zwirner
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000276:immunology; D018920:Coculture Techniques; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D006801:Humans; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D000099192:CD69 Antigens
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D050822:Cytokine Receptor gp130; D020382:Interleukin-18; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D037181:Lectins, C-Type; D011994:Recombinant Proteins; D000099192:CD69 Antigens; C000589760:IL18 protein, human; C508017:IL2RA protein, human; C494199:IL6ST protein, human; C464565:MYDGF protein, human
keywords: Cytotoxicity; IFN-γ; IL-18; IL-27; NK cells