Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation

Dendritic cells (DCs) are antigen (Ag)-presenting cells that activate and stimulate effective immune responses by T cells, but can also act as negative regulators of these responses and thus play important roles in immune regulation. Pro-angiogenic vascular endothelial growth factor (VEGF) has been...

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Autores: Marti, Luciana Cavalheiro, Pavon, Lorena, Severino, Patricia, Sibov, Tatiana, Guilhen, Daiane, Moreira-Filho, Carlos Alberto
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Brasil
Recursos:Universidade Federal de São Paulo (UNIFESP)
Repositorio:Repositório Institucional da UNIFESP
Idioma:inglés
OAI Identifier:oai:repositorio.unifesp.br:11600/37349
Acesso em linha:http://dx.doi.org/10.1590/0074-0276130252
http://repositorio.unifesp.br/handle/11600/37349
Access Level:acceso abierto
Palavra-chave:indoleamine-pyrrole 2,3-dioxygenase
dendritic cell
vascular endothelial growth factor A
tolerance
immune
lymphocytes
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spelling Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferationindoleamine-pyrrole 2,3-dioxygenasedendritic cellvascular endothelial growth factor AtoleranceimmunelymphocytesDendritic cells (DCs) are antigen (Ag)-presenting cells that activate and stimulate effective immune responses by T cells, but can also act as negative regulators of these responses and thus play important roles in immune regulation. Pro-angiogenic vascular endothelial growth factor (VEGF) has been shown to cause defective DC differentiation and maturation. Previous studies have demonstrated that the addition of VEGF to DC cultures renders these cells weak stimulators of Ag-specific T cells due to the inhibitory effects mediated by VEGF receptor 1 (VEGFR1) and/or VEGFR2 signalling. As the enzyme indoleamine 2,3-dioxygenase (IDO) is recognised as an important negative regulator of immune responses, this study aimed to investigate whether VEGF affects the expression of IDO by DCs and whether VEGF-matured DCs acquire a suppressor phenotype. Our results are the first to demonstrate that VEGF increases the expression and activity of IDO in DCs, which has a suppressive effect on Ag-specific and mitogen-stimulated lymphocyte proliferation. These mechanisms have broad implications for the study of immunological responses and tolerance under conditions as diverse as cancer, graft rejection and autoimmunity.Inst Israelita Ensino & Pesquisa Albert Einstein, Ctr Pesquisa Expt, São Paulo, BrazilHosp Israelita Albert Einstein, Inst Cerebro, Ctr Pesquisa Expt, São Paulo, BrazilUniv São Paulo, Fac Med, Dept Pediat, São Paulo, BrazilWeb of ScienceSBIBHIAEFundaco Oswaldo CruzInst Israelita Ensino & Pesquisa Albert EinsteinHosp Israelita Albert EinsteinUniversidade Federal de São Paulo (UNIFESP)2016-01-24T14:35:11Z2016-01-24T14:35:11Z2014-02-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion70-79application/pdfhttp://dx.doi.org/10.1590/0074-0276130252Memorias Do Instituto Oswaldo Cruz. Rio de Janeiro, Rj: Fundaco Oswaldo Cruz, v. 109, n. 1, p. 70-79, 2014.10.1590/0074-0276130252S0074-02762014000100070.pdf0074-0276S0074-02762014000100070http://repositorio.unifesp.br/handle/11600/37349WOS:000333038700009ark:/48912/001300002n5rjengMemorias Do Instituto Oswaldo Cruzinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPMarti, Luciana CavalheiroPavon, LorenaSeverino, PatriciaSibov, TatianaGuilhen, DaianeMoreira-Filho, Carlos Alberto2024-08-08T05:22:28Zoai:repositorio.unifesp.br:11600/37349Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-08T05:22:28Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
title Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
spellingShingle Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
Marti, Luciana Cavalheiro
indoleamine-pyrrole 2,3-dioxygenase
dendritic cell
vascular endothelial growth factor A
tolerance
immune
lymphocytes
title_short Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
title_full Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
title_fullStr Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
title_full_unstemmed Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
title_sort Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation
dc.creator.none.fl_str_mv Marti, Luciana Cavalheiro
Pavon, Lorena
Severino, Patricia
Sibov, Tatiana
Guilhen, Daiane
Moreira-Filho, Carlos Alberto
author Marti, Luciana Cavalheiro
author_facet Marti, Luciana Cavalheiro
Pavon, Lorena
Severino, Patricia
Sibov, Tatiana
Guilhen, Daiane
Moreira-Filho, Carlos Alberto
author_role author
author2 Pavon, Lorena
Severino, Patricia
Sibov, Tatiana
Guilhen, Daiane
Moreira-Filho, Carlos Alberto
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Inst Israelita Ensino & Pesquisa Albert Einstein
Hosp Israelita Albert Einstein
Universidade Federal de São Paulo (UNIFESP)
dc.subject.por.fl_str_mv indoleamine-pyrrole 2,3-dioxygenase
dendritic cell
vascular endothelial growth factor A
tolerance
immune
lymphocytes
topic indoleamine-pyrrole 2,3-dioxygenase
dendritic cell
vascular endothelial growth factor A
tolerance
immune
lymphocytes
description Dendritic cells (DCs) are antigen (Ag)-presenting cells that activate and stimulate effective immune responses by T cells, but can also act as negative regulators of these responses and thus play important roles in immune regulation. Pro-angiogenic vascular endothelial growth factor (VEGF) has been shown to cause defective DC differentiation and maturation. Previous studies have demonstrated that the addition of VEGF to DC cultures renders these cells weak stimulators of Ag-specific T cells due to the inhibitory effects mediated by VEGF receptor 1 (VEGFR1) and/or VEGFR2 signalling. As the enzyme indoleamine 2,3-dioxygenase (IDO) is recognised as an important negative regulator of immune responses, this study aimed to investigate whether VEGF affects the expression of IDO by DCs and whether VEGF-matured DCs acquire a suppressor phenotype. Our results are the first to demonstrate that VEGF increases the expression and activity of IDO in DCs, which has a suppressive effect on Ag-specific and mitogen-stimulated lymphocyte proliferation. These mechanisms have broad implications for the study of immunological responses and tolerance under conditions as diverse as cancer, graft rejection and autoimmunity.
publishDate 2014
dc.date.none.fl_str_mv 2014-02-01
2016-01-24T14:35:11Z
2016-01-24T14:35:11Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1590/0074-0276130252
Memorias Do Instituto Oswaldo Cruz. Rio de Janeiro, Rj: Fundaco Oswaldo Cruz, v. 109, n. 1, p. 70-79, 2014.
10.1590/0074-0276130252
S0074-02762014000100070.pdf
0074-0276
S0074-02762014000100070
http://repositorio.unifesp.br/handle/11600/37349
WOS:000333038700009
dc.identifier.dark.fl_str_mv ark:/48912/001300002n5rj
url http://dx.doi.org/10.1590/0074-0276130252
http://repositorio.unifesp.br/handle/11600/37349
identifier_str_mv Memorias Do Instituto Oswaldo Cruz. Rio de Janeiro, Rj: Fundaco Oswaldo Cruz, v. 109, n. 1, p. 70-79, 2014.
10.1590/0074-0276130252
S0074-02762014000100070.pdf
0074-0276
S0074-02762014000100070
WOS:000333038700009
ark:/48912/001300002n5rj
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Memorias Do Instituto Oswaldo Cruz
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 70-79
application/pdf
dc.publisher.none.fl_str_mv Fundaco Oswaldo Cruz
publisher.none.fl_str_mv Fundaco Oswaldo Cruz
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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