IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness

Autores
Ziblat, Andrea; Domaica, Carolina Ines; Spallanzani, Raúl Germán; Raffo Iraolagoitia, Ximena Lucía; Rossi, Lucas Ezequiel; Avila, Damian Ezequiel Gualberto; Torres, Nicolás; Fuertes, Mercedes Beatriz; Zwirner, Norberto Walter
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remain unknown. In this study, we observed that mature dendritic cells (mDCs) secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their coculture, showing the importance of IL-27 during DC?NK-cell cross-talk. Accordingly, human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion which was associated with an IL-27-driven upregulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK cell-mediated cytotoxicity against Raji, T-47D and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK-cell-mediated cytotoxicity involved upregulation of perforin (pfp), granule exocytosis and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent NK-cell-mediated cytotoxicity (ADCC) against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations.
Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología, Parasitología e Inmunología.; Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Spallanzani, Raúl Germán. 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: 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 Cs.exactas. Departamento de Cs.biologicas. Catedra de Inmunologia; Argentina
Fil: Torres, Nicolás. 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: Fuertes, Mercedes Beatriz. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); 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. Departamento de Microbiología, Parasitología e Inmunología; Argentina
Materia
Cytotoxicity
Ifn-Gamma
Il-18
Il-27
Nk Cells
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:11336/6294
Acceder
id CONICETDig_c36325eaa89efb8224bc6f05cd7b6810
oai_identifier_str oai:ri.conicet.gov.ar:11336/6294
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsivenessZiblat, AndreaDomaica, Carolina InesSpallanzani, Raúl GermánRaffo Iraolagoitia, Ximena LucíaRossi, Lucas EzequielAvila, Damian Ezequiel GualbertoTorres, NicolásFuertes, Mercedes BeatrizZwirner, Norberto WalterCytotoxicityIfn-GammaIl-18Il-27Nk Cellshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remain unknown. In this study, we observed that mature dendritic cells (mDCs) secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their coculture, showing the importance of IL-27 during DC?NK-cell cross-talk. Accordingly, human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion which was associated with an IL-27-driven upregulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK cell-mediated cytotoxicity against Raji, T-47D and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK-cell-mediated cytotoxicity involved upregulation of perforin (pfp), granule exocytosis and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent NK-cell-mediated cytotoxicity (ADCC) against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations.Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología, Parasitología e Inmunología.; ArgentinaFil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Spallanzani, Raúl Germán. 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: 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 Cs.exactas. Departamento de Cs.biologicas. Catedra de Inmunologia; ArgentinaFil: Torres, Nicolás. 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: Fuertes, Mercedes Beatriz. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); 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. Departamento de Microbiología, Parasitología e Inmunología; ArgentinaWiley2015-01-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6294Ziblat, Andrea; Domaica, Carolina Ines; Spallanzani, Raúl Germán; Raffo Iraolagoitia, Ximena Lucía; Rossi, Lucas Ezequiel; et al.; IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness; Wiley; European Journal of Immunology; 45; 1; 13-1-2015; 192-2020014-29801521-4141enginfo:eu-repo/semantics/altIdentifier/doi/10.1002/eji.201444699info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201444699/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:44Zoai:ri.conicet.gov.ar:11336/6294instacron: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 09:53:45.244CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
spellingShingle IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
Ziblat, Andrea
Cytotoxicity
Ifn-Gamma
Il-18
Il-27
Nk Cells
title_short IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_full IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_fullStr IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_full_unstemmed IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
title_sort IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness
dc.creator.none.fl_str_mv Ziblat, Andrea
Domaica, Carolina Ines
Spallanzani, Raúl Germán
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Avila, Damian Ezequiel Gualberto
Torres, Nicolás
Fuertes, Mercedes Beatriz
Zwirner, Norberto Walter
author Ziblat, Andrea
author_facet Ziblat, Andrea
Domaica, Carolina Ines
Spallanzani, Raúl Germán
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Avila, Damian Ezequiel Gualberto
Torres, Nicolás
Fuertes, Mercedes Beatriz
Zwirner, Norberto Walter
author_role author
author2 Domaica, Carolina Ines
Spallanzani, Raúl Germán
Raffo Iraolagoitia, Ximena Lucía
Rossi, Lucas Ezequiel
Avila, Damian Ezequiel Gualberto
Torres, Nicolás
Fuertes, Mercedes Beatriz
Zwirner, Norberto Walter
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cytotoxicity
Ifn-Gamma
Il-18
Il-27
Nk Cells
topic Cytotoxicity
Ifn-Gamma
Il-18
Il-27
Nk Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remain unknown. In this study, we observed that mature dendritic cells (mDCs) secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their coculture, showing the importance of IL-27 during DC?NK-cell cross-talk. Accordingly, human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion which was associated with an IL-27-driven upregulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK cell-mediated cytotoxicity against Raji, T-47D and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK-cell-mediated cytotoxicity involved upregulation of perforin (pfp), granule exocytosis and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent NK-cell-mediated cytotoxicity (ADCC) against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations.
Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología, Parasitología e Inmunología.; Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Spallanzani, Raúl Germán. 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: 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 Cs.exactas. Departamento de Cs.biologicas. Catedra de Inmunologia; Argentina
Fil: Torres, Nicolás. 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: Fuertes, Mercedes Beatriz. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); 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. Departamento de Microbiología, Parasitología e Inmunología; Argentina
description IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displays pro- and anti-inflammatory effects. How IL-27 affects human NK cells still remain unknown. In this study, we observed that mature dendritic cells (mDCs) secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their coculture, showing the importance of IL-27 during DC?NK-cell cross-talk. Accordingly, human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion which was associated with an IL-27-driven upregulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK cell-mediated cytotoxicity against Raji, T-47D and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK-cell-mediated cytotoxicity involved upregulation of perforin (pfp), granule exocytosis and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent NK-cell-mediated cytotoxicity (ADCC) against mAb-coated target cells. Taken together, IL-27 stimulates NK-cell effector functions, which might be relevant in different physiological and pathological situations.
publishDate 2015
dc.date.none.fl_str_mv 2015-01-13
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/11336/6294
Ziblat, Andrea; Domaica, Carolina Ines; Spallanzani, Raúl Germán; Raffo Iraolagoitia, Ximena Lucía; Rossi, Lucas Ezequiel; et al.; IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness; Wiley; European Journal of Immunology; 45; 1; 13-1-2015; 192-202
0014-2980
1521-4141
url http://hdl.handle.net/11336/6294
identifier_str_mv Ziblat, Andrea; Domaica, Carolina Ines; Spallanzani, Raúl Germán; Raffo Iraolagoitia, Ximena Lucía; Rossi, Lucas Ezequiel; et al.; IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness; Wiley; European Journal of Immunology; 45; 1; 13-1-2015; 192-202
0014-2980
1521-4141
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201444699/abstract
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
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dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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
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