IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness

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 remain unknown. In this study, we observed that mature dendritic cells (mDCs) secreted IL-27 and that blockade of IL-27R (CD130) reduced the...

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Detalles Bibliográficos
Autores: Ziblat, Andrea, Domaica, Carolina Ines, Spallanzani, Raúl Germán, Raffo Iraolagoitia, Ximena Lucía, Rossi, Lucas Ezequiel, Avila, Damian Ezequiel Gualberto, Torres, Nicolás, Fuertes, Mercedes Beatriz, Zwirner, Norberto Walter
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/6294
Acceso en línea:http://hdl.handle.net/11336/6294
Access Level:acceso abierto
Palabra clave:Cytotoxicity
Ifn-Gamma
Il-18
Il-27
Nk Cells
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario: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 remain unknown. In this study, we observed that mature dendritic cells (mDCs) 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 cross-talk. 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 (pfp), granule exocytosis and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent NK-cell-mediated cytotoxicity (ADCC) against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations.

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