IL-27 promotes IFN- secretion and cytotoxicity of human NK cells

ZIBLAT ANDREA; DOMAICA CAROLINA I.; RAFFO I. XIMENA L.; SPALLANZANI RAÚL G.; FUERTES MERCEDES B.; ZWIRNER NORBERTO W.

Otro; First Spring Course in Advanced Immunology; 2013

Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI) de la Escuela de Posgrado de la Facultad de Ciencias Químicas de la Universidad de Córdoba

NK cells express IL-27R but the effects of IL-27 (mainly produced by dendritic cells ?DCs?) on human NK cells remain unknown. In this work we investigated this subject using NK cells stimulated with IL-27 and/or IL-18 in the presence of IL-15 (as survival factor). We observed that IL-27 stimulated the production of IFN-g (assessed by ELISA) due to a priming effect for IL-18 (p<0,01) that did not involve NK cell proliferation. Conversely, IL-27 exhibited an anti-proliferative effect on NK cells either in the absence or in the presence of IL-18 (p<0,05) that was not due to a decreased NK cell viability. Also, IL-27 induced a significant up-regulation of CD69 (p<0,05) and NKp46 (p<0,001). Accordingly, IL-27 stimulated NKp46-dependent cytotoxicity (assessed by flow cytometry with CFSE-labeled target cells and 7-AAD staining) against Raji cells, either alone (p<0,001) or in combination with IL-18 (p<0,05). The mechanisms underlying such cytotoxic response involved the secretory pathway (it was inhibited by concanamycin A), TRAIL (but not Fas-FasL) pathway, and a cooperative effect mediated by IFN-g secreted by NK cells (demonstrated using blocking antibodies). Therefore, we conclude that IL-27 induces NK cell activation and primes NK cells for IL-18-mediated IFN-g secretion, which could be relevant during the cross-talk with DCs. In addition, IL-27 stimulates NKp46-dependent cytotoxicity, which may contribute to the elimination of virus-infected and tumor cells. Overall, our results indicate that IL-27 (a cytokine that has pro- and anti-inflammatory effects) exerts a potent stimulatory effect on NK cell effector functions.