Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors

Autores
Spallanzani, Raúl Germán; Torres, Nicolás; Avila, Damian Ezequiel Gualberto; Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; Rossi, Lucas Ezequiel; Domaica, Carolina Ines; 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-g 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-g 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-g 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-gamma, 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.
Fil: Spallanzani, Raúl Germán. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Avila, Damian Ezequiel Gualberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rossi, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Materia
Regulatory Dendritic Cells
Nk Cells
Ifn-G
Nkp46
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/10177
Acceder
id CONICETDig_89d093cb2391916bddf8222b85d2e74b
oai_identifier_str oai:ri.conicet.gov.ar:11336/10177
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptorsSpallanzani, Raúl GermánTorres, NicolásAvila, Damian Ezequiel GualbertoZiblat, AndreaRaffo Iraolagoitia, Ximena LucíaRossi, Lucas EzequielDomaica, Carolina InesFuertes, Mercedes BeatrizRabinovich, Gabriel AdriánZwirner, Norberto WalterRegulatory Dendritic CellsNk CellsIfn-GNkp46https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cross-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-g 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-g 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-g 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-gamma, 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.Fil: Spallanzani, Raúl Germán. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Avila, Damian Ezequiel Gualberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rossi, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaAmer Assoc Immunologists2015-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10177Spallanzani, Raúl Germán; Torres, Nicolás; Avila, Damian Ezequiel Gualberto; Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; et al.; Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors; Amer Assoc Immunologists; Journal Of Immunology; 195; 5; 1-9-2015; 2141-21480022-17671550-6606enginfo:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/195/5/2141.longinfo:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1403161info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:31Zoai:ri.conicet.gov.ar:11336/10177instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:06:31.295CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
title Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
spellingShingle Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
Spallanzani, Raúl Germán
Regulatory Dendritic Cells
Nk Cells
Ifn-G
Nkp46
title_short Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
title_full Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
title_fullStr Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
title_full_unstemmed Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
title_sort Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors
dc.creator.none.fl_str_mv Spallanzani, Raúl Germán
Torres, Nicolás
Avila, Damian Ezequiel Gualberto
Ziblat, Andrea
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Domaica, Carolina Ines
Fuertes, Mercedes Beatriz
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
author Spallanzani, Raúl Germán
author_facet Spallanzani, Raúl Germán
Torres, Nicolás
Avila, Damian Ezequiel Gualberto
Ziblat, Andrea
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Domaica, Carolina Ines
Fuertes, Mercedes Beatriz
Rabinovich, Gabriel Adrián
Zwirner, Norberto Walter
author_role author
author2 Torres, Nicolás
Avila, Damian Ezequiel Gualberto
Ziblat, Andrea
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Domaica, Carolina Ines
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 Regulatory Dendritic Cells
Nk Cells
Ifn-G
Nkp46
topic Regulatory Dendritic Cells
Nk Cells
Ifn-G
Nkp46
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
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-g 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-g 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-g 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-gamma, 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.
Fil: Spallanzani, Raúl Germán. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Avila, Damian Ezequiel Gualberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rossi, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
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-g 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-g 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-g 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-gamma, 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 2015-09-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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://hdl.handle.net/11336/10177
Spallanzani, Raúl Germán; Torres, Nicolás; Avila, Damian Ezequiel Gualberto; Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; et al.; Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors; Amer Assoc Immunologists; Journal Of Immunology; 195; 5; 1-9-2015; 2141-2148
0022-1767
1550-6606
url http://hdl.handle.net/11336/10177
identifier_str_mv Spallanzani, Raúl Germán; Torres, Nicolás; Avila, Damian Ezequiel Gualberto; Ziblat, Andrea; Raffo Iraolagoitia, Ximena Lucía; et al.; Regulatory Dendritic Cells restrain NK cell IFN-g production through mechanisms involving NKp46, IL-10 and MHC class I-specific inhibitory receptors; Amer Assoc Immunologists; Journal Of Immunology; 195; 5; 1-9-2015; 2141-2148
0022-1767
1550-6606
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/195/5/2141.long
info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1403161
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Amer Assoc Immunologists
publisher.none.fl_str_mv Amer Assoc Immunologists
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269962082713600
score 13.13397

Publicaciones similares