Artículo

Spallanzani, R.G.; Torres, N.I.; Avila, D.E.; Ziblat, A.; Raffo Iraolagoitia, X.L.; Rossi, L.E.; Domaica, C.I.; Fuertes, M.B.; Rabinovich, G.A.; Zwirner, N.W. "Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors" (2015) Journal of Immunology. 195(5):2141-2148
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Abstract:

Cross-talk between mature dendritic cells (mDC) and NK cells through the cell surface receptors NKp30 and DNAM-1 leads to their reciprocal activation. However, the impact of regulatory dendritic cells (regDC) on NK cell function remains unknown. As regDC constrain the immune response in different physiological and pathological conditions, the aim of this work was to investigate the functional outcome of the interaction between regDC and NK cells and the associated underlying mechanisms. RegDC generated from monocyte-derived DC treated either with LPS and dexamethasone, vitamin D3, or vitamin D3 and dexamethasone instructed NK cells to secrete lower amounts of IFN-γ than NK cells exposed to mDC. Although regDC triggered upregulation of the activation markers CD69 and CD25 on NK cells, they did not induce upregulation of CD56 as mDC, and silenced IFN-γ secretion through mechanisms involving insufficient secretion of IL-18, but not IL-12 or IL-15 and/or induction of NK cell apoptosis. Blocking experiments demonstrated that regDC curb IFN-γ secretion by NK cells through a dominant suppressive mechanism involving IL-10, NK cell inhibitory receptors, and, unexpectedly, engagement of the activating receptor NKp46. Our findings unveil a previously unrecognized cross-talk through which regDC shape NK cell function toward an alternative activated phenotype unable to secrete IFN-γ, highlighting the plasticity of NK cells in response to tolerogenic stimuli. In addition, our findings contribute to identify a novel inhibitory role for NKp46 in the control of NK cell function, and have broad implications in the resolution of inflammatory responses and evasion of antitumor responses. Copyright © 2015 by The American Association of Immunologists, Inc.

Registro:

Documento: Artículo
Título:Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
Autor:Spallanzani, R.G.; Torres, N.I.; Avila, D.E.; Ziblat, A.; Raffo Iraolagoitia, X.L.; Rossi, L.E.; Domaica, C.I.; Fuertes, M.B.; Rabinovich, G.A.; Zwirner, N.W.
Filiación:Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, Buenos Aires, C1428ADN, Argentina
Cátedra de Inmunología, Facultad de Ciencias Exactas, Universidad Nacional de la Plata, La Plata, 1900, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, C1428ADN, Argentina
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, C1121ABG, Argentina
Palabras clave:CD69 antigen; colecalciferol; dexamethasone; gamma interferon; interleukin 10; interleukin 12; interleukin 15; interleukin 18; interleukin 2 receptor alpha; lipopolysaccharide; major histocompatibility antigen class 1; natural cytotoxicity triggering receptor 1; colecalciferol; dexamethasone; gamma interferon; glucocorticoid; HLA antigen class 1; interleukin 10; interleukin 12; interleukin 18; lipopolysaccharide; natural cytotoxicity triggering receptor 1; T lymphocyte receptor; vitamin; apoptosis; Article; cell function; cell interaction; controlled study; cytokine production; cytokine release; dendritic cell; human; human cell; lymphocyte function; natural killer cell; priority journal; upregulation; biosynthesis; cell communication; cell culture; dendritic cell; drug effects; flow cytometry; immunology; metabolism; secretion (process); signal transduction; Cell Communication; Cells, Cultured; Cholecalciferol; Costimulatory and Inhibitory T-Cell Receptors; Dendritic Cells; Dexamethasone; Flow Cytometry; Glucocorticoids; Histocompatibility Antigens Class I; Humans; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-18; Killer Cells, Natural; Lipopolysaccharides; Natural Cytotoxicity Triggering Receptor 1; Receptor Cross-Talk; Vitamins
Año:2015
Volumen:195
Número:5
Página de inicio:2141
Página de fin:2148
DOI: http://dx.doi.org/10.4049/jimmunol.1403161
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
ISSN:00221767
CODEN:JOIMA
CAS:colecalciferol, 1406-16-2, 67-97-0; dexamethasone, 50-02-2; gamma interferon, 82115-62-6; interleukin 12, 138415-13-1; interleukin 18, 189304-55-0; Cholecalciferol; Costimulatory and Inhibitory T-Cell Receptors; Dexamethasone; Glucocorticoids; Histocompatibility Antigens Class I; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-18; Lipopolysaccharides; Natural Cytotoxicity Triggering Receptor 1; Vitamins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v195_n5_p2141_Spallanzani

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Citas:

---------- APA ----------
Spallanzani, R.G., Torres, N.I., Avila, D.E., Ziblat, A., Raffo Iraolagoitia, X.L., Rossi, L.E., Domaica, C.I.,..., Zwirner, N.W. (2015) . Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors. Journal of Immunology, 195(5), 2141-2148.
http://dx.doi.org/10.4049/jimmunol.1403161
---------- CHICAGO ----------
Spallanzani, R.G., Torres, N.I., Avila, D.E., Ziblat, A., Raffo Iraolagoitia, X.L., Rossi, L.E., et al. "Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors" . Journal of Immunology 195, no. 5 (2015) : 2141-2148.
http://dx.doi.org/10.4049/jimmunol.1403161
---------- MLA ----------
Spallanzani, R.G., Torres, N.I., Avila, D.E., Ziblat, A., Raffo Iraolagoitia, X.L., Rossi, L.E., et al. "Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors" . Journal of Immunology, vol. 195, no. 5, 2015, pp. 2141-2148.
http://dx.doi.org/10.4049/jimmunol.1403161
---------- VANCOUVER ----------
Spallanzani, R.G., Torres, N.I., Avila, D.E., Ziblat, A., Raffo Iraolagoitia, X.L., Rossi, L.E., et al. Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors. J. Immunol. 2015;195(5):2141-2148.
http://dx.doi.org/10.4049/jimmunol.1403161