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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/130244

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network_name_str CONICET Digital (CONICET)
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
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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
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publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
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