Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition

ABSTRACT:Background and aims: B cells involvement in animal models of atherosclerosis has been unequivocally established. However, the role of these cells in patients with atherosclerosis is almost unknown. Besides the production of antibodies, B cells can also exhibit regulatory functions mainly th...

Full description

Autores:
Rincón Arévalo, Héctor Julián
Quintero Hurtado, Julio César
Fortich Hoyos, Fernando Manuel
Rojas López, Mauricio
Vásquez Duque, Gloria María
Castaño Monsalve, Diana María
Yassin Noreña, Lina María
Tipo de recurso:
Article of investigation
Fecha de publicación:
2020
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/42300
Acceso en línea:
https://hdl.handle.net/10495/42300
Palabra clave:
Aterosclerosis
Atherosclerosis
Subgrupos de Linfocitos B
B-Lymphocyte Subsets
Linfocitos B
B-Lymphocytes
Proteína C-Reactiva
C-Reactive Protein
Colesterol
Cholesterol
Sistema Cardiovascular
Cardiovascular System
Interleucina-10
Interleukin-10
Enfermedades del Sistema Inmune
Immune System Diseases
Sistema Inmunológico
Immune System
Linfocitos B Reguladores
B-Lymphocytes, Regulatory
Inflamación
Inflammation
https://id.nlm.nih.gov/mesh/D050197
https://id.nlm.nih.gov/mesh/D016175
https://id.nlm.nih.gov/mesh/D001402
https://id.nlm.nih.gov/mesh/D002097
https://id.nlm.nih.gov/mesh/D002784
https://id.nlm.nih.gov/mesh/D002319
https://id.nlm.nih.gov/mesh/D016753
https://id.nlm.nih.gov/mesh/D007154
https://id.nlm.nih.gov/mesh/D007107
https://id.nlm.nih.gov/mesh/D060151
https://id.nlm.nih.gov/mesh/D007249
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
id UDEA2_6ade64b8c99f97790f57c7d27b3d6632
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/42300
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
title Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
spellingShingle Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
Aterosclerosis
Atherosclerosis
Subgrupos de Linfocitos B
B-Lymphocyte Subsets
Linfocitos B
B-Lymphocytes
Proteína C-Reactiva
C-Reactive Protein
Colesterol
Cholesterol
Sistema Cardiovascular
Cardiovascular System
Interleucina-10
Interleukin-10
Enfermedades del Sistema Inmune
Immune System Diseases
Sistema Inmunológico
Immune System
Linfocitos B Reguladores
B-Lymphocytes, Regulatory
Inflamación
Inflammation
https://id.nlm.nih.gov/mesh/D050197
https://id.nlm.nih.gov/mesh/D016175
https://id.nlm.nih.gov/mesh/D001402
https://id.nlm.nih.gov/mesh/D002097
https://id.nlm.nih.gov/mesh/D002784
https://id.nlm.nih.gov/mesh/D002319
https://id.nlm.nih.gov/mesh/D016753
https://id.nlm.nih.gov/mesh/D007154
https://id.nlm.nih.gov/mesh/D007107
https://id.nlm.nih.gov/mesh/D060151
https://id.nlm.nih.gov/mesh/D007249
title_short Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
title_full Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
title_fullStr Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
title_full_unstemmed Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
title_sort Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition
dc.creator.fl_str_mv Rincón Arévalo, Héctor Julián
Quintero Hurtado, Julio César
Fortich Hoyos, Fernando Manuel
Rojas López, Mauricio
Vásquez Duque, Gloria María
Castaño Monsalve, Diana María
Yassin Noreña, Lina María
dc.contributor.author.none.fl_str_mv Rincón Arévalo, Héctor Julián
Quintero Hurtado, Julio César
Fortich Hoyos, Fernando Manuel
Rojas López, Mauricio
Vásquez Duque, Gloria María
Castaño Monsalve, Diana María
Yassin Noreña, Lina María
dc.contributor.researchgroup.spa.fl_str_mv Grupo de Inmunología Celular e Inmunogenética
dc.subject.decs.none.fl_str_mv Aterosclerosis
Atherosclerosis
Subgrupos de Linfocitos B
B-Lymphocyte Subsets
Linfocitos B
B-Lymphocytes
Proteína C-Reactiva
C-Reactive Protein
Colesterol
Cholesterol
Sistema Cardiovascular
Cardiovascular System
Interleucina-10
Interleukin-10
Enfermedades del Sistema Inmune
Immune System Diseases
Sistema Inmunológico
Immune System
Linfocitos B Reguladores
B-Lymphocytes, Regulatory
Inflamación
Inflammation
topic Aterosclerosis
Atherosclerosis
Subgrupos de Linfocitos B
B-Lymphocyte Subsets
Linfocitos B
B-Lymphocytes
Proteína C-Reactiva
C-Reactive Protein
Colesterol
Cholesterol
Sistema Cardiovascular
Cardiovascular System
Interleucina-10
Interleukin-10
Enfermedades del Sistema Inmune
Immune System Diseases
Sistema Inmunológico
Immune System
Linfocitos B Reguladores
B-Lymphocytes, Regulatory
Inflamación
Inflammation
https://id.nlm.nih.gov/mesh/D050197
https://id.nlm.nih.gov/mesh/D016175
https://id.nlm.nih.gov/mesh/D001402
https://id.nlm.nih.gov/mesh/D002097
https://id.nlm.nih.gov/mesh/D002784
https://id.nlm.nih.gov/mesh/D002319
https://id.nlm.nih.gov/mesh/D016753
https://id.nlm.nih.gov/mesh/D007154
https://id.nlm.nih.gov/mesh/D007107
https://id.nlm.nih.gov/mesh/D060151
https://id.nlm.nih.gov/mesh/D007249
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D050197
https://id.nlm.nih.gov/mesh/D016175
https://id.nlm.nih.gov/mesh/D001402
https://id.nlm.nih.gov/mesh/D002097
https://id.nlm.nih.gov/mesh/D002784
https://id.nlm.nih.gov/mesh/D002319
https://id.nlm.nih.gov/mesh/D016753
https://id.nlm.nih.gov/mesh/D007154
https://id.nlm.nih.gov/mesh/D007107
https://id.nlm.nih.gov/mesh/D060151
https://id.nlm.nih.gov/mesh/D007249
description ABSTRACT:Background and aims: B cells involvement in animal models of atherosclerosis has been unequivocally established. However, the role of these cells in patients with atherosclerosis is almost unknown. Besides the production of antibodies, B cells can also exhibit regulatory functions mainly through IL-10. Here, we characterized human B cell subsets, their production of IL-10 in patients with atherosclerosis and their potential association with inflammation. Methods: Patients with confirmed atherosclerotic events and controls with low cardiovascular risk were included. B cells subsets were determined in mononuclear cells (PBMC) using flow cytometry. PBMC were cultured ex vivo (5 h) and in vitro (48 h) to determine IL-10+ B cells and in some cases TNF-α+ and IFN-γ+ CD4+ T cells. The inflammatory state of the participants was determined through high sensitivity C reactive protein levels. Results: Increase in percentage and number of plasmablasts was observed in patients with atherosclerosis compared with controls. A decreased frequency of IL-10+ B cells was observed in patients, both in ex vivo and in vitro cultures. This decrease was detected in transitional, memory, and plasmablast subsets. Interestingly, the reduction of IL-10+ B cells negatively and significantly correlated with the inflammatory condition of the studied subjects and associated with an increased frequency of TNF-α+ and IFN-γ+ CD4+ T cells. The blockade of IL-10R did not show further effect in T cells activation. Conclusions: There is an association between the inflammatory state and a reduction of IL-10+ B cells that could contribute to the development of atherosclerosis.
publishDate 2020
dc.date.issued.none.fl_str_mv 2020
dc.date.accessioned.none.fl_str_mv 2024-09-20T15:18:33Z
dc.date.available.none.fl_str_mv 2024-09-20T15:18:33Z
dc.type.spa.fl_str_mv Artículo de investigación
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.citation.spa.fl_str_mv Rincón-Arévalo H, Quintero JC, Fortich F, Rojas M, Vásquez G, Castaño D, Yassin LM. Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition. Heliyon. 2020 Mar 3;6(3):e03441. doi: 10.1016/j.heliyon.2020.e03441.
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/42300
dc.identifier.doi.none.fl_str_mv 10.1016/j.heliyon.2020.e03441
dc.identifier.eissn.none.fl_str_mv 2405-8440
identifier_str_mv Rincón-Arévalo H, Quintero JC, Fortich F, Rojas M, Vásquez G, Castaño D, Yassin LM. Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition. Heliyon. 2020 Mar 3;6(3):e03441. doi: 10.1016/j.heliyon.2020.e03441.
10.1016/j.heliyon.2020.e03441
2405-8440
url https://hdl.handle.net/10495/42300
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Heliyon
dc.relation.citationendpage.spa.fl_str_mv 9
dc.relation.citationissue.spa.fl_str_mv 3
dc.relation.citationstartpage.spa.fl_str_mv 1
dc.relation.citationvolume.spa.fl_str_mv 6
dc.relation.ispartofjournal.spa.fl_str_mv Heliyon
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
https://creativecommons.org/licenses/by-nc-nd/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 9 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Elsevier
dc.publisher.place.spa.fl_str_mv Londres, Inglaterra
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstreams/bfae3a5d-207b-4fd2-818f-46484f0ee5a8/download
https://bibliotecadigital.udea.edu.co/bitstreams/29c7adad-7403-41e7-baf8-9c36d0d97b7a/download
https://bibliotecadigital.udea.edu.co/bitstreams/73ef3fd2-4da7-4eda-88ca-384fa9dcc71d/download
https://bibliotecadigital.udea.edu.co/bitstreams/6c0f0586-52dc-4dac-adb0-2f046898715d/download
https://bibliotecadigital.udea.edu.co/bitstreams/bf0fca17-a330-4815-86f2-36962eb36fda/download
bitstream.checksum.fl_str_mv eb004557e99cd887a0f4d15fc1437a3d
b88b088d9957e670ce3b3fbe2eedbc13
8a4605be74aa9ea9d79846c1fba20a33
7c7eecd0175e12aab3657661f0d13e86
435e8870798e41a02a089640d542c21d
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional de la Universidad de Antioquia
repository.mail.fl_str_mv aplicacionbibliotecadigitalbiblioteca@udea.edu.co
_version_ 1851052571818459136
spelling Rincón Arévalo, Héctor JuliánQuintero Hurtado, Julio CésarFortich Hoyos, Fernando ManuelRojas López, MauricioVásquez Duque, Gloria MaríaCastaño Monsalve, Diana MaríaYassin Noreña, Lina MaríaGrupo de Inmunología Celular e Inmunogenética2024-09-20T15:18:33Z2024-09-20T15:18:33Z2020Rincón-Arévalo H, Quintero JC, Fortich F, Rojas M, Vásquez G, Castaño D, Yassin LM. Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition. Heliyon. 2020 Mar 3;6(3):e03441. doi: 10.1016/j.heliyon.2020.e03441.https://hdl.handle.net/10495/4230010.1016/j.heliyon.2020.e034412405-8440ABSTRACT:Background and aims: B cells involvement in animal models of atherosclerosis has been unequivocally established. However, the role of these cells in patients with atherosclerosis is almost unknown. Besides the production of antibodies, B cells can also exhibit regulatory functions mainly through IL-10. Here, we characterized human B cell subsets, their production of IL-10 in patients with atherosclerosis and their potential association with inflammation. Methods: Patients with confirmed atherosclerotic events and controls with low cardiovascular risk were included. B cells subsets were determined in mononuclear cells (PBMC) using flow cytometry. PBMC were cultured ex vivo (5 h) and in vitro (48 h) to determine IL-10+ B cells and in some cases TNF-α+ and IFN-γ+ CD4+ T cells. The inflammatory state of the participants was determined through high sensitivity C reactive protein levels. Results: Increase in percentage and number of plasmablasts was observed in patients with atherosclerosis compared with controls. A decreased frequency of IL-10+ B cells was observed in patients, both in ex vivo and in vitro cultures. This decrease was detected in transitional, memory, and plasmablast subsets. Interestingly, the reduction of IL-10+ B cells negatively and significantly correlated with the inflammatory condition of the studied subjects and associated with an increased frequency of TNF-α+ and IFN-γ+ CD4+ T cells. The blockade of IL-10R did not show further effect in T cells activation. Conclusions: There is an association between the inflammatory state and a reduction of IL-10+ B cells that could contribute to the development of atherosclerosis.Universidad de Antioquia. Vicerrectoría de investigación. Comité para el Desarrollo de la Investigación - CODIColombia. Ministerio de Ciencia, Tecnología e Innovación - MinCienciasCOL00086399 páginasapplication/pdfengElsevierLondres, Inglaterrahttp://creativecommons.org/licenses/by-nc-nd/2.5/co/https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory conditionArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAterosclerosisAtherosclerosisSubgrupos de Linfocitos BB-Lymphocyte SubsetsLinfocitos BB-LymphocytesProteína C-ReactivaC-Reactive ProteinColesterolCholesterolSistema CardiovascularCardiovascular SystemInterleucina-10Interleukin-10Enfermedades del Sistema InmuneImmune System DiseasesSistema InmunológicoImmune SystemLinfocitos B ReguladoresB-Lymphocytes, RegulatoryInflamaciónInflammationhttps://id.nlm.nih.gov/mesh/D050197https://id.nlm.nih.gov/mesh/D016175https://id.nlm.nih.gov/mesh/D001402https://id.nlm.nih.gov/mesh/D002097https://id.nlm.nih.gov/mesh/D002784https://id.nlm.nih.gov/mesh/D002319https://id.nlm.nih.gov/mesh/D016753https://id.nlm.nih.gov/mesh/D007154https://id.nlm.nih.gov/mesh/D007107https://id.nlm.nih.gov/mesh/D060151https://id.nlm.nih.gov/mesh/D007249Heliyon9316HeliyonPrograma Jóvenes InvestigadoresMinCiencias 111554431390RoR:03bp5hc83RoR:03fd5ne08PublicationORIGINALRojasMauricio_2020_Low_Frequency_IL-10.pdfRojasMauricio_2020_Low_Frequency_IL-10.pdfArtículo de investigaciónapplication/pdf2407628https://bibliotecadigital.udea.edu.co/bitstreams/bfae3a5d-207b-4fd2-818f-46484f0ee5a8/downloadeb004557e99cd887a0f4d15fc1437a3dMD54trueAnonymousREADCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8823https://bibliotecadigital.udea.edu.co/bitstreams/29c7adad-7403-41e7-baf8-9c36d0d97b7a/downloadb88b088d9957e670ce3b3fbe2eedbc13MD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/73ef3fd2-4da7-4eda-88ca-384fa9dcc71d/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADTEXTRojasMauricio_2020_Low_Frequency_IL-10.pdf.txtRojasMauricio_2020_Low_Frequency_IL-10.pdf.txtExtracted texttext/plain54234https://bibliotecadigital.udea.edu.co/bitstreams/6c0f0586-52dc-4dac-adb0-2f046898715d/download7c7eecd0175e12aab3657661f0d13e86MD55falseAnonymousREADTHUMBNAILRojasMauricio_2020_Low_Frequency_IL-10.pdf.jpgRojasMauricio_2020_Low_Frequency_IL-10.pdf.jpgGenerated Thumbnailimage/jpeg14298https://bibliotecadigital.udea.edu.co/bitstreams/bf0fca17-a330-4815-86f2-36962eb36fda/download435e8870798e41a02a089640d542c21dMD56falseAnonymousREAD10495/42300oai:bibliotecadigital.udea.edu.co:10495/423002025-03-27 00:28:56.074http://creativecommons.org/licenses/by-nc-nd/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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