Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors

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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 ph...

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Detalles Bibliográficos
Autores principales: Spallanzani, Raúl Germán, Torres, N. I., Ávila, Damián Ezequiel, Ziblat, Andrea, Raffo Iraolagoitia, Ximena Lucía, Rossi, Lucas Ezequiel, Domaica, Carolina Inés, Fuertes, Mercedes Beatriz, Rabinovich, Gabriel Adrián, Zwirner, Norberto Walter
Formato: Articulo
Lenguaje:Inglés
Publicado: 2015
Materias:
Ciencias Exactas
Inmumología
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/87319
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-87319
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Inmumología
spellingShingle Ciencias Exactas
Inmumología
Spallanzani, Raúl Germán
Torres, N. I.
Ávila, Damián Ezequiel
Ziblat, Andrea
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Domaica, Carolina Inés
Fuertes, Mercedes Beatriz
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
topic_facet Ciencias Exactas
Inmumología
description 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.
format Articulo
Articulo
author Spallanzani, Raúl Germán
Torres, N. I.
Ávila, Damián Ezequiel
Ziblat, Andrea
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Domaica, Carolina Inés
Fuertes, Mercedes Beatriz
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
author_facet Spallanzani, Raúl Germán
Torres, N. I.
Ávila, Damián Ezequiel
Ziblat, Andrea
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Domaica, Carolina Inés
Fuertes, Mercedes Beatriz
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
author_sort Spallanzani, Raúl Germán
title Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
title_short Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
title_full Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
title_fullStr Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
title_full_unstemmed Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
title_sort regulatory dendritic cells restrain nk cell ifn-γ production through mechanisms involving nkp46, il-10, and mhc class i-specific inhibitory receptors
publishDate 2015
url http://sedici.unlp.edu.ar/handle/10915/87319
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