PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment

Autores
Zacca, Estefanía; Onofrio, Luisina Inés; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Alonso, Sergio Manuel; Ramello, María Cecilia; Mussano, Eduardo Daniel Eugenio; Onetti, Laura; Cadile, Isaac I.; Stancich, Maria I.; Bonfanti, Maria C. Taboada; Montes, Carolina Lucia; Acosta Rodriguez, Eva Virginia; Gruppi, Adriana
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.
Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Onofrio, Luisina Inés. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Acosta, Cristina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Ferrero, Paola Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Alonso, Sergio Manuel. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Mussano, Eduardo Daniel Eugenio. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Onetti, Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Cadile, Isaac I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Stancich, Maria I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Bonfanti, Maria C. Taboada. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
BREGS
INFLAMMATION
PD-L1
RHEUMATIC DISEASES
RHEUMATOID ARTHRITIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/95869
Acceder
id CONICETDig_d4ce85e2dcd95948d5d4cf308afc0f33
oai_identifier_str oai:ri.conicet.gov.ar:11336/95869
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful TreatmentZacca, EstefaníaOnofrio, Luisina InésAcosta, Cristina del ValleFerrero, Paola VirginiaAlonso, Sergio ManuelRamello, María CeciliaMussano, Eduardo Daniel EugenioOnetti, LauraCadile, Isaac I.Stancich, Maria I.Bonfanti, Maria C. TaboadaMontes, Carolina LuciaAcosta Rodriguez, Eva VirginiaGruppi, AdrianaBREGSINFLAMMATIONPD-L1RHEUMATIC DISEASESRHEUMATOID ARTHRITIShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Onofrio, Luisina Inés. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Acosta, Cristina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Ferrero, Paola Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Alonso, Sergio Manuel. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Mussano, Eduardo Daniel Eugenio. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Onetti, Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Cadile, Isaac I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Stancich, Maria I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Bonfanti, Maria C. Taboada. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFrontiers Media S.A.2018-10info: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/11336/95869Zacca, Estefanía; Onofrio, Luisina Inés; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Alonso, Sergio Manuel; et al.; PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment; Frontiers Media S.A.; Frontiers in Immunology; 9; 10-2018; 1-131664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2018.02241/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02241info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:42:49Zoai:ri.conicet.gov.ar:11336/95869instacron: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:34982025-09-29 10:42:49.669CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
title PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
spellingShingle PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
Zacca, Estefanía
BREGS
INFLAMMATION
PD-L1
RHEUMATIC DISEASES
RHEUMATOID ARTHRITIS
title_short PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
title_full PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
title_fullStr PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
title_full_unstemmed PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
title_sort PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
dc.creator.none.fl_str_mv Zacca, Estefanía
Onofrio, Luisina Inés
Acosta, Cristina del Valle
Ferrero, Paola Virginia
Alonso, Sergio Manuel
Ramello, María Cecilia
Mussano, Eduardo Daniel Eugenio
Onetti, Laura
Cadile, Isaac I.
Stancich, Maria I.
Bonfanti, Maria C. Taboada
Montes, Carolina Lucia
Acosta Rodriguez, Eva Virginia
Gruppi, Adriana
author Zacca, Estefanía
author_facet Zacca, Estefanía
Onofrio, Luisina Inés
Acosta, Cristina del Valle
Ferrero, Paola Virginia
Alonso, Sergio Manuel
Ramello, María Cecilia
Mussano, Eduardo Daniel Eugenio
Onetti, Laura
Cadile, Isaac I.
Stancich, Maria I.
Bonfanti, Maria C. Taboada
Montes, Carolina Lucia
Acosta Rodriguez, Eva Virginia
Gruppi, Adriana
author_role author
author2 Onofrio, Luisina Inés
Acosta, Cristina del Valle
Ferrero, Paola Virginia
Alonso, Sergio Manuel
Ramello, María Cecilia
Mussano, Eduardo Daniel Eugenio
Onetti, Laura
Cadile, Isaac I.
Stancich, Maria I.
Bonfanti, Maria C. Taboada
Montes, Carolina Lucia
Acosta Rodriguez, Eva Virginia
Gruppi, Adriana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BREGS
INFLAMMATION
PD-L1
RHEUMATIC DISEASES
RHEUMATOID ARTHRITIS
topic BREGS
INFLAMMATION
PD-L1
RHEUMATIC DISEASES
RHEUMATOID ARTHRITIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.
Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Onofrio, Luisina Inés. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Acosta, Cristina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Ferrero, Paola Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Alonso, Sergio Manuel. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Mussano, Eduardo Daniel Eugenio. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Onetti, Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Cadile, Isaac I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Stancich, Maria I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Bonfanti, Maria C. Taboada. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
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/11336/95869
Zacca, Estefanía; Onofrio, Luisina Inés; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Alonso, Sergio Manuel; et al.; PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment; Frontiers Media S.A.; Frontiers in Immunology; 9; 10-2018; 1-13
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95869
identifier_str_mv Zacca, Estefanía; Onofrio, Luisina Inés; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Alonso, Sergio Manuel; et al.; PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment; Frontiers Media S.A.; Frontiers in Immunology; 9; 10-2018; 1-13
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2018.02241/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02241
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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_ 1844614461716955136
score 13.070432

Publicaciones similares