Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors
- Autores
- 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
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Facultad de Ciencias Exactas - Materia
-
Ciencias Exactas
Inmumología - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/87319
Ver los metadatos del registro completo
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Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptorsSpallanzani, Raúl GermánTorres, N. I.Ávila, Damián EzequielZiblat, AndreaRaffo Iraolagoitia, Ximena LucíaRossi, Lucas EzequielDomaica, Carolina InésFuertes, Mercedes BeatrizRabinovich, Gabriel AdriánZwirner, Norberto WalterCiencias ExactasInmumologíaCross-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.Facultad de Ciencias Exactas2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf2141-2148http://sedici.unlp.edu.ar/handle/10915/87319enginfo:eu-repo/semantics/altIdentifier/issn/0022-1767info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1403161info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:16:59Zoai:sedici.unlp.edu.ar:10915/87319Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:59.484SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
title |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors |
spellingShingle |
Regulatory dendritic cells restrain NK cell IFN-γ production through mechanisms involving NKp46, IL-10, and MHC class I-specific inhibitory receptors Spallanzani, Raúl Germán Ciencias Exactas Inmumología |
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 |
dc.creator.none.fl_str_mv |
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 |
Spallanzani, Raúl Germán |
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_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
Ciencias Exactas Inmumología |
topic |
Ciencias Exactas Inmumología |
dc.description.none.fl_txt_mv |
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. Facultad de Ciencias Exactas |
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. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://sedici.unlp.edu.ar/handle/10915/87319 |
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http://sedici.unlp.edu.ar/handle/10915/87319 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/issn/0022-1767 info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1403161 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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openAccess |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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