Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j
- Autores
- Nuñez, Sol Yanel; Ziblat, Andrea; Secchiari, Florencia; Torres, Nicolás; Sierra, Jessica Mariel; Raffo Iraolagoitia, Ximena Lucía; Araya, Romina Elizabeth; Domaica, Carolina Ines; Fuertes, Mercedes Beatriz; Zwirner, Norberto Walter
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete pro-inflammatory cytokines such as IFN-g. In addition, upon activation, macrophages can become pro-inflammatory (M1) or anti inflammatory (M2) cells. Although the consequences of the crosstalk between M1 and NK cells are known, the outcome of the crosstalk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN-g upon co-culture with M2. Also, CD56dim NK cells co-cultured with M2 displayed lower degranulation and cytotoxic activity than NK cells co-cultured with M1. Soluble TGF-b and M2-driven up-regulation of CD85j (ILT-2)on NK cells accounted for the diminished IFN-g production by CD56bright NK cells, while M2-driven up-regulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56dim NK cells with limited degranulation and cytotoxic capacity. Accordingly, M2 expressed higher amounts of HLA-G, the main ligand for CD85j, than M1. Hyporesponsiveness to degranulation in NK cells was not restored at least for several hours upon removal of M2. Therefore, alternatively-activated macrophages restrain NK cell activation and effector functions through different mechanisms, leading to NK cells that display diminished IFN-g production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations.
Fil: Nuñez, Sol Yanel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sierra, Jessica Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Araya, Romina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina - Materia
-
Macrophages
Nk Cells
Immunosurveillance
Cytotoxicity
Ifn-G - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/41268
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spelling |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85jNuñez, Sol YanelZiblat, AndreaSecchiari, FlorenciaTorres, NicolásSierra, Jessica MarielRaffo Iraolagoitia, Ximena LucíaAraya, Romina ElizabethDomaica, Carolina InesFuertes, Mercedes BeatrizZwirner, Norberto WalterMacrophagesNk CellsImmunosurveillanceCytotoxicityIfn-Ghttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete pro-inflammatory cytokines such as IFN-g. In addition, upon activation, macrophages can become pro-inflammatory (M1) or anti inflammatory (M2) cells. Although the consequences of the crosstalk between M1 and NK cells are known, the outcome of the crosstalk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN-g upon co-culture with M2. Also, CD56dim NK cells co-cultured with M2 displayed lower degranulation and cytotoxic activity than NK cells co-cultured with M1. Soluble TGF-b and M2-driven up-regulation of CD85j (ILT-2)on NK cells accounted for the diminished IFN-g production by CD56bright NK cells, while M2-driven up-regulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56dim NK cells with limited degranulation and cytotoxic capacity. Accordingly, M2 expressed higher amounts of HLA-G, the main ligand for CD85j, than M1. Hyporesponsiveness to degranulation in NK cells was not restored at least for several hours upon removal of M2. Therefore, alternatively-activated macrophages restrain NK cell activation and effector functions through different mechanisms, leading to NK cells that display diminished IFN-g production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations.Fil: Nuñez, Sol Yanel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sierra, Jessica Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Araya, Romina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaAmerican Association of Immunologists2018-02-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41268Nuñez, Sol Yanel; Ziblat, Andrea; Secchiari, Florencia; Torres, Nicolás; Sierra, Jessica Mariel; et al.; Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j; American Association of Immunologists; Journal of Immunology; 200; 3; 1-2-2018; 1008-10150022-17671550-6606CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.1700737info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1700737info:eu-repo/semantics/altIdentifier/pmid/29282306info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:19Zoai:ri.conicet.gov.ar:11336/41268instacron: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 09:47:19.46CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
title |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
spellingShingle |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j Nuñez, Sol Yanel Macrophages Nk Cells Immunosurveillance Cytotoxicity Ifn-G |
title_short |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
title_full |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
title_fullStr |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
title_full_unstemmed |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
title_sort |
Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j |
dc.creator.none.fl_str_mv |
Nuñez, Sol Yanel Ziblat, Andrea Secchiari, Florencia Torres, Nicolás Sierra, Jessica Mariel Raffo Iraolagoitia, Ximena Lucía Araya, Romina Elizabeth Domaica, Carolina Ines Fuertes, Mercedes Beatriz Zwirner, Norberto Walter |
author |
Nuñez, Sol Yanel |
author_facet |
Nuñez, Sol Yanel Ziblat, Andrea Secchiari, Florencia Torres, Nicolás Sierra, Jessica Mariel Raffo Iraolagoitia, Ximena Lucía Araya, Romina Elizabeth Domaica, Carolina Ines Fuertes, Mercedes Beatriz Zwirner, Norberto Walter |
author_role |
author |
author2 |
Ziblat, Andrea Secchiari, Florencia Torres, Nicolás Sierra, Jessica Mariel Raffo Iraolagoitia, Ximena Lucía Araya, Romina Elizabeth Domaica, Carolina Ines Fuertes, Mercedes Beatriz Zwirner, Norberto Walter |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
Macrophages Nk Cells Immunosurveillance Cytotoxicity Ifn-G |
topic |
Macrophages Nk Cells Immunosurveillance Cytotoxicity Ifn-G |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete pro-inflammatory cytokines such as IFN-g. In addition, upon activation, macrophages can become pro-inflammatory (M1) or anti inflammatory (M2) cells. Although the consequences of the crosstalk between M1 and NK cells are known, the outcome of the crosstalk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN-g upon co-culture with M2. Also, CD56dim NK cells co-cultured with M2 displayed lower degranulation and cytotoxic activity than NK cells co-cultured with M1. Soluble TGF-b and M2-driven up-regulation of CD85j (ILT-2)on NK cells accounted for the diminished IFN-g production by CD56bright NK cells, while M2-driven up-regulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56dim NK cells with limited degranulation and cytotoxic capacity. Accordingly, M2 expressed higher amounts of HLA-G, the main ligand for CD85j, than M1. Hyporesponsiveness to degranulation in NK cells was not restored at least for several hours upon removal of M2. Therefore, alternatively-activated macrophages restrain NK cell activation and effector functions through different mechanisms, leading to NK cells that display diminished IFN-g production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations. Fil: Nuñez, Sol Yanel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Secchiari, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Torres, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Sierra, Jessica Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Raffo Iraolagoitia, Ximena Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Araya, Romina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina |
description |
NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete pro-inflammatory cytokines such as IFN-g. In addition, upon activation, macrophages can become pro-inflammatory (M1) or anti inflammatory (M2) cells. Although the consequences of the crosstalk between M1 and NK cells are known, the outcome of the crosstalk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN-g upon co-culture with M2. Also, CD56dim NK cells co-cultured with M2 displayed lower degranulation and cytotoxic activity than NK cells co-cultured with M1. Soluble TGF-b and M2-driven up-regulation of CD85j (ILT-2)on NK cells accounted for the diminished IFN-g production by CD56bright NK cells, while M2-driven up-regulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56dim NK cells with limited degranulation and cytotoxic capacity. Accordingly, M2 expressed higher amounts of HLA-G, the main ligand for CD85j, than M1. Hyporesponsiveness to degranulation in NK cells was not restored at least for several hours upon removal of M2. Therefore, alternatively-activated macrophages restrain NK cell activation and effector functions through different mechanisms, leading to NK cells that display diminished IFN-g production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-02-01 |
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/11336/41268 Nuñez, Sol Yanel; Ziblat, Andrea; Secchiari, Florencia; Torres, Nicolás; Sierra, Jessica Mariel; et al.; Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j; American Association of Immunologists; Journal of Immunology; 200; 3; 1-2-2018; 1008-1015 0022-1767 1550-6606 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/41268 |
identifier_str_mv |
Nuñez, Sol Yanel; Ziblat, Andrea; Secchiari, Florencia; Torres, Nicolás; Sierra, Jessica Mariel; et al.; Human M2 macrophages limit NK cell effector functions through secretion of TGF-b and engagement of CD85j; American Association of Immunologists; Journal of Immunology; 200; 3; 1-2-2018; 1008-1015 0022-1767 1550-6606 CONICET Digital CONICET |
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/lookup/doi/10.4049/jimmunol.1700737 info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1700737 info:eu-repo/semantics/altIdentifier/pmid/29282306 |
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 |
dc.publisher.none.fl_str_mv |
American Association of Immunologists |
publisher.none.fl_str_mv |
American Association of 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 |
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1842268850568036352 |
score |
13.13397 |