MERTK as negative regulator of human T cell activation

Autores
Cabezón, Raquel; Carrera Silva, Eugenio Antonio; Flórez Grau, Georgina; Errasti, Andrea Emilse; Calderón Gómez, Elisabeth; Lozano, Juan José; España, Carolina; Ricart, Elena; Panés, Julián; Rothlin, Carla; Benítez Ribas, Daniel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whetherMERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol- DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction withMERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.
Fil: Cabezón, Raquel. Fundacio Clínic per a la Recerca Biomèdica; España
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Flórez Grau, Georgina. Institut d’Investigacions Biomèdiques August Pi i Sunyer; España
Fil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Calderón Gómez, Elisabeth. Institut d’Investigacions Biomèdiques August Pi i Sunyer; España
Fil: Lozano, Juan José. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
Fil: España, Carolina. Fundació Clínic per a la Recerca Biomèdica; España
Fil: Ricart, Elena. Hospital Clínic de Barcelona; España
Fil: Panés, Julián. Hospital Clínic de Barcelona; España
Fil: Rothlin, Carla. University of Yale; Estados Unidos
Fil: Benítez Ribas, Daniel. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
Materia
SUPPRESSION
TAM RECEPTORS
TOLEROGENIC DENDRITIC 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:11336/16239
Acceder
id CONICETDig_6e980fd713e081867e1bf224086c4cf8
oai_identifier_str oai:ri.conicet.gov.ar:11336/16239
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MERTK as negative regulator of human T cell activationCabezón, RaquelCarrera Silva, Eugenio AntonioFlórez Grau, GeorginaErrasti, Andrea EmilseCalderón Gómez, ElisabethLozano, Juan JoséEspaña, CarolinaRicart, ElenaPanés, JuliánRothlin, CarlaBenítez Ribas, DanielSUPPRESSIONTAM RECEPTORSTOLEROGENIC DENDRITIC CELLShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whetherMERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol- DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction withMERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.Fil: Cabezón, Raquel. Fundacio Clínic per a la Recerca Biomèdica; EspañaFil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Flórez Grau, Georgina. Institut d’Investigacions Biomèdiques August Pi i Sunyer; EspañaFil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Calderón Gómez, Elisabeth. Institut d’Investigacions Biomèdiques August Pi i Sunyer; EspañaFil: Lozano, Juan José. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; EspañaFil: España, Carolina. Fundació Clínic per a la Recerca Biomèdica; EspañaFil: Ricart, Elena. Hospital Clínic de Barcelona; EspañaFil: Panés, Julián. Hospital Clínic de Barcelona; EspañaFil: Rothlin, Carla. University of Yale; Estados UnidosFil: Benítez Ribas, Daniel. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; EspañaFederation of American Societies for Experimental Biology2015-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16239Cabezón, Raquel; Carrera Silva, Eugenio Antonio; Flórez Grau, Georgina; Errasti, Andrea Emilse; Calderón Gómez, Elisabeth; et al.; MERTK as negative regulator of human T cell activation; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 97; 4; 4-2015; 751-7600741-5400enginfo:eu-repo/semantics/altIdentifier/doi/10.1189/jlb.3A0714-334Rinfo:eu-repo/semantics/altIdentifier/url/http://www.jleukbio.org/content/97/4/751.fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:52:50Zoai:ri.conicet.gov.ar:11336/16239instacron: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:34982025-10-22 11:52:51.158CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MERTK as negative regulator of human T cell activation
title MERTK as negative regulator of human T cell activation
spellingShingle MERTK as negative regulator of human T cell activation
Cabezón, Raquel
SUPPRESSION
TAM RECEPTORS
TOLEROGENIC DENDRITIC CELLS
title_short MERTK as negative regulator of human T cell activation
title_full MERTK as negative regulator of human T cell activation
title_fullStr MERTK as negative regulator of human T cell activation
title_full_unstemmed MERTK as negative regulator of human T cell activation
title_sort MERTK as negative regulator of human T cell activation
dc.creator.none.fl_str_mv Cabezón, Raquel
Carrera Silva, Eugenio Antonio
Flórez Grau, Georgina
Errasti, Andrea Emilse
Calderón Gómez, Elisabeth
Lozano, Juan José
España, Carolina
Ricart, Elena
Panés, Julián
Rothlin, Carla
Benítez Ribas, Daniel
author Cabezón, Raquel
author_facet Cabezón, Raquel
Carrera Silva, Eugenio Antonio
Flórez Grau, Georgina
Errasti, Andrea Emilse
Calderón Gómez, Elisabeth
Lozano, Juan José
España, Carolina
Ricart, Elena
Panés, Julián
Rothlin, Carla
Benítez Ribas, Daniel
author_role author
author2 Carrera Silva, Eugenio Antonio
Flórez Grau, Georgina
Errasti, Andrea Emilse
Calderón Gómez, Elisabeth
Lozano, Juan José
España, Carolina
Ricart, Elena
Panés, Julián
Rothlin, Carla
Benítez Ribas, Daniel
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SUPPRESSION
TAM RECEPTORS
TOLEROGENIC DENDRITIC CELLS
topic SUPPRESSION
TAM RECEPTORS
TOLEROGENIC DENDRITIC CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whetherMERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol- DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction withMERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.
Fil: Cabezón, Raquel. Fundacio Clínic per a la Recerca Biomèdica; España
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Flórez Grau, Georgina. Institut d’Investigacions Biomèdiques August Pi i Sunyer; España
Fil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Calderón Gómez, Elisabeth. Institut d’Investigacions Biomèdiques August Pi i Sunyer; España
Fil: Lozano, Juan José. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
Fil: España, Carolina. Fundació Clínic per a la Recerca Biomèdica; España
Fil: Ricart, Elena. Hospital Clínic de Barcelona; España
Fil: Panés, Julián. Hospital Clínic de Barcelona; España
Fil: Rothlin, Carla. University of Yale; Estados Unidos
Fil: Benítez Ribas, Daniel. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
description The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whetherMERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol- DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction withMERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response.
publishDate 2015
dc.date.none.fl_str_mv 2015-04
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/11336/16239
Cabezón, Raquel; Carrera Silva, Eugenio Antonio; Flórez Grau, Georgina; Errasti, Andrea Emilse; Calderón Gómez, Elisabeth; et al.; MERTK as negative regulator of human T cell activation; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 97; 4; 4-2015; 751-760
0741-5400
url http://hdl.handle.net/11336/16239
identifier_str_mv Cabezón, Raquel; Carrera Silva, Eugenio Antonio; Flórez Grau, Georgina; Errasti, Andrea Emilse; Calderón Gómez, Elisabeth; et al.; MERTK as negative regulator of human T cell activation; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 97; 4; 4-2015; 751-760
0741-5400
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1189/jlb.3A0714-334R
info:eu-repo/semantics/altIdentifier/url/http://www.jleukbio.org/content/97/4/751.full
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
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
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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score 12.982451

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