Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01959
Keywords
natural killer cells; interleukin-23; interleukin-18; IFN-gamma; dendritic cells
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Funding
- National Agency for Promotion of Science and Technology from Argentina (ANPCYT)
- National Research Council of Argentina (CONICET)
- University of Buenos Aires (UBA)
- Fundacion Williams
- Fundacion Rene Baron
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Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it is also involved in the development of autoimmune diseases. Although immunoregulatory effects of IL-23 on mouse natural killer (NK) cells have been described, the effect of IL-23 on human NK cells remains ill-defined. In this study, we observed that monocytes stimulated with LPS secreted IL-23 and that blockade of this cytokine during monocyte and NK cell coculture led to a diminished production of IFN-gamma by NK cells. Accordingly, rIL-23-induced NK cell activation and stimulated IFN-gamma production by CD56(bright) NK cells. This effect involved MEK1/MEK2, JNK, PI3K, mammalian target of rapamycin, and NF-kappa B, but not STAT-1, STAT-3, nor p38 MAPK pathways. Moreover, while NK cell-mediated cytotoxicity remained unaltered, antibody-dependent cellular cytotoxicity (ADCC) was enhanced after IL-23 stimulation. In addition, IL-23 displayed a synergistic effect with IL-18 for IFN-gamma production by both CD56(bright) and CD56(dim) NK cells, and this effect was due to a priming effect of IL-23 for IL-18 responsiveness. Furthermore, NK cells pre-stimulated with IL-18 promoted an increase in CD86 expression and IL-12 secretion by DC treated with LPS, and IL-23 potentiated these effects. Moreover, IL-23-driven enhancement of NK cell helper function was dependent on NK cell-derived IFN-gamma. Therefore, our results suggest that IL-23 may trigger NK cell-mediated helper effects on adaptive immunity, shaping T cell responses during different pathological situations through the regulation of DC maturation.
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