IL-23 promotes NK cell activation and IFN-γ secretion

RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; TORRES, NICOLÁS IGNACIO; ARAYA, ROMINA ELIZABETH; ZIBLAT, ANDREA; NÚÑEZ, SOL YANEL; SIERRA, JESSICA MARIEL; ZWIRNER, NORBERTO WALTER; SPALLANZANI, RAÚL GERMÁN; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ

Melbourne

Congreso; ICI2016. International Congress of Immunology; 2016

International Union of Immunological Societies (IUIS)

IL-23 is a member of the IL-12 family of cytokines thatin mice has been shown to display pro- and anti-tumor activities. AlthoughIL-23 is secreted by mature dendritic cells (mDC) and mDC play a crucial roleduring NK cell activation, the role of IL-23 on human NK cells remains poorlyexplored. Thus, the goal of this work was to elucidate the effect of IL-23 on peripheralblood human NK cells isolated from healthy donors. We observed that indeed DCstimulated with LPS secreted IL-23. Moreover, co-cultures of LPS-activated DCswith NK cells in the presence of anti-IL-23 blocking antibodies markedlydiminished IFN-g secretion by NKcells. In addition, recombinant IL-23 induced the secretion of IFN-g by both resting and activated NK cells. Furthermore,the use of pharmacological inhibitors showed that JNK, PI3K, MEK1/2, NF-kB andm-TOR -but not the p38 MAP kinase, JAK-STAT3 and STAT-1- were involved in thisresponse. Also, IL-23 significantly up-regulated CD25 and CD69 and had apriming effect for IL-18-mediated secretion of IFN-g. Besides, although IL-23 did not alter the cytotoxiccapacity of NK cells against Raji cells, we observed an increase ofantibody-dependent cellular cytotoxicity (ADCC) of IL-23-stimulated NK cellsagainst Rituximab-coated Raji cells. Overall, these results demonstrate thatIL-23 -alone or in combination with IL-18- exerts a potent stimulatory effecton IFN-g secretion byhuman NK cells, expanding the current knowledge on the role of IL-23 during theDC-NK cell cross-talk and on NK cell-mediated immunity.