B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy
- Autores
- Zacca, Estefanía; Amezcua Vesely, Maria Carolina; Ferrero, P. V.; Acosta, Cristina del Valle; Ponce, Nicolás Eric; Bossio, Sabrina Noemí; Mussano, Eduardo Daniel Eugenio; Onetti, Laura Beatriz; Cadile, I.; Acosta Rodriguez, Eva Virginia; Montes, Carolina Lucia; Gruppi, Adriana
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA.
Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hosp.nacional de Clinicas. Laboratorio de Inmunología y Serología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Amezcua Vesely, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ferrero, P. V.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Acosta, Cristina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Bossio, Sabrina Noemí. 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 Beatriz. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Cadile, I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; 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: Montes, Carolina Lucia. 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
-
ADO PATHWAY
BREG
CD39
RHEUMATHOID ARTHRITIS
T-CELL SUPPRESSION - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/130244
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/130244 |
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spelling |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapyZacca, EstefaníaAmezcua Vesely, Maria CarolinaFerrero, P. V.Acosta, Cristina del VallePonce, Nicolás EricBossio, Sabrina NoemíMussano, Eduardo Daniel EugenioOnetti, Laura BeatrizCadile, I.Acosta Rodriguez, Eva VirginiaMontes, Carolina LuciaGruppi, AdrianaADO PATHWAYBREGCD39RHEUMATHOID ARTHRITIST-CELL SUPPRESSIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA.Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hosp.nacional de Clinicas. Laboratorio de Inmunología y Serología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Amezcua Vesely, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ferrero, P. V.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Acosta, Cristina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bossio, Sabrina Noemí. 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 Beatriz. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Cadile, I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; 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: Montes, Carolina Lucia. 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; ArgentinaAcademic Press Ltd - Elsevier Science Ltd2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130244Zacca, Estefanía; Amezcua Vesely, Maria Carolina; Ferrero, P. V.; Acosta, Cristina del Valle; Ponce, Nicolás Eric; et al.; B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 433; 1; 1-2021; 1-110022-2836CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0022283620305969info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmb.2020.10.021info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:29:07Zoai:ri.conicet.gov.ar:11336/130244instacron: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:34982025-10-15 15:29:07.722CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy |
title |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy |
spellingShingle |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy Zacca, Estefanía ADO PATHWAY BREG CD39 RHEUMATHOID ARTHRITIS T-CELL SUPPRESSION |
title_short |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy |
title_full |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy |
title_fullStr |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy |
title_full_unstemmed |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy |
title_sort |
B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy |
dc.creator.none.fl_str_mv |
Zacca, Estefanía Amezcua Vesely, Maria Carolina Ferrero, P. V. Acosta, Cristina del Valle Ponce, Nicolás Eric Bossio, Sabrina Noemí Mussano, Eduardo Daniel Eugenio Onetti, Laura Beatriz Cadile, I. Acosta Rodriguez, Eva Virginia Montes, Carolina Lucia Gruppi, Adriana |
author |
Zacca, Estefanía |
author_facet |
Zacca, Estefanía Amezcua Vesely, Maria Carolina Ferrero, P. V. Acosta, Cristina del Valle Ponce, Nicolás Eric Bossio, Sabrina Noemí Mussano, Eduardo Daniel Eugenio Onetti, Laura Beatriz Cadile, I. Acosta Rodriguez, Eva Virginia Montes, Carolina Lucia Gruppi, Adriana |
author_role |
author |
author2 |
Amezcua Vesely, Maria Carolina Ferrero, P. V. Acosta, Cristina del Valle Ponce, Nicolás Eric Bossio, Sabrina Noemí Mussano, Eduardo Daniel Eugenio Onetti, Laura Beatriz Cadile, I. Acosta Rodriguez, Eva Virginia Montes, Carolina Lucia Gruppi, Adriana |
author2_role |
author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
ADO PATHWAY BREG CD39 RHEUMATHOID ARTHRITIS T-CELL SUPPRESSION |
topic |
ADO PATHWAY BREG CD39 RHEUMATHOID ARTHRITIS T-CELL SUPPRESSION |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA. Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hosp.nacional de Clinicas. Laboratorio de Inmunología y Serología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Amezcua Vesely, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Ferrero, P. V.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Acosta, Cristina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Bossio, Sabrina Noemí. 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 Beatriz. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Cadile, I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; 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: Montes, Carolina Lucia. 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 |
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01 |
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/11336/130244 Zacca, Estefanía; Amezcua Vesely, Maria Carolina; Ferrero, P. V.; Acosta, Cristina del Valle; Ponce, Nicolás Eric; et al.; B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 433; 1; 1-2021; 1-11 0022-2836 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/130244 |
identifier_str_mv |
Zacca, Estefanía; Amezcua Vesely, Maria Carolina; Ferrero, P. V.; Acosta, Cristina del Valle; Ponce, Nicolás Eric; et al.; B cells from patients with rheumatoid arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 433; 1; 1-2021; 1-11 0022-2836 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://linkinghub.elsevier.com/retrieve/pii/S0022283620305969 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmb.2020.10.021 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Academic Press Ltd - Elsevier Science Ltd |
publisher.none.fl_str_mv |
Academic Press Ltd - Elsevier Science Ltd |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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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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13.22299 |