IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Coss-talk with regulatory dendritic cells promotes NK cell activation towards an alternative phenotype characterized by low secretion of IFN-γ
Autor/es:
TORRES, NICOLÁS IGNACIO; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; SIERRA, JESSICA MARIEL; FUERTES, MERCEDES BEATRIZ; ZIBLAT, ANDREA; NÚÑEZ, SOL YANEL; DOMAICA, CAROLINA INÉS; SPALLANZANI, RAÚL GERMÁN; ARAYA, ROMINA ELIZABETH; SECCHIARI, FLORENCIA; ZWIRNER, NORBERTO WALTER
Lugar:
Melbourne
Reunión:
Congreso; ICI2016. International Congress of Immunology; 2016
Institución organizadora:
International Union of Immunological Societies (IUIS)
Resumen:
Background:The functional consequences of the interaction between dendritic cells (DC) andNK cells play an essential role during the immune responses againstvirus-infected cells and tumors. In addition, tumor microenvironment promotesthe expansion of regulatory dendritic cells (regDC), which may contribute toimmune escape. As little is known about the consequences of the crosstalkbetween regDC and NK cells, the aim of this work was to explore the outcome ofsuch crosstalk and to unravel the underlying mechanisms. Methods: Human NK cells and monocytes were isolated from blood.Monocytes were cultured for 6 d with GM-CSF and IL-4 to obtain immature DC(iDC). Then, iDC were stimulated with LPS to obtain mature DC (mDC) or LPS anddexamethasone, vitamin D3 or their combination to obtain regDC. Results: NK cells co-cultured withregDC or mDC upregulated the activation markers CD69 and CD25. However, NKcells co-cultured with regDC did not up-regulate CD56 as NK cells co-culturedwith mDC. Also, NK cells co-cultured with regDC secreted lower amounts of IFN-g than NK cells exposed to mDC, an effect that was in part due to insufficientsecretion of IL-18, but not IL-12 or IL-15 and/or induction of NK cellapoptosis. Blocking experiments demonstrated that regDC curb IFN-g secretion by NK cells through a dominant suppressive mechanisminvolving IL-10, inhibitory receptors and unexpectedly, engagement of theactivating receptor NKp46. Conclusions:Our findings identify an inhibitory role of regDC, and describe a novelinhibitory function for NKp46 in the control of NK cell function.