Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice

Detalhes bibliográficos
Autor(a) principal: Duarte, Joana
Data de Publicação: 2010
Outros Autores: Agua-Doce, Ana, Oliveira, Vanessa G., Fonseca, João Eurico, Graca, Luis
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/6033
Resumo: ©2010 Duarte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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spelling Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in miceRheumatoid arthritisTh 17Treg cellsFoxp3Antigens, CD4©2010 Duarte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells. Methodology and Findings: We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice – a recently described animal model of RA – by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction. Conclusions: Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.This work was funded by SUDOE, grant number IMMUNONET-SOE1/1P1/E014, and supported by a research grant from Fundação para a Ciência e Tecnologia (FCT), Portugal (FCT/POCI/SAU-MMO/55974/2004). JD, AA-D, and VGO are funded with scholarships from FCT (SFRH/BD/23631/2005, SFRH/BD/49093/2008, and SFRH/BPD/22575/2005).Public Library of ScienceRepositório da Universidade de LisboaDuarte, JoanaAgua-Doce, AnaOliveira, Vanessa G.Fonseca, João EuricoGraca, Luis2012-04-18T16:02:44Z2010-052010-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/6033engPLoS ONE | May 2010 | Volume 5 | Issue 5 | e105581932-620310.1371/journal.pone.0010558info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:48:15Zoai:repositorio.ul.pt:10451/6033Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:31:15.705505Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
title Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
spellingShingle Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
Duarte, Joana
Rheumatoid arthritis
Th 17
Treg cells
Foxp3
Antigens, CD4
title_short Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
title_full Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
title_fullStr Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
title_full_unstemmed Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
title_sort Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice
author Duarte, Joana
author_facet Duarte, Joana
Agua-Doce, Ana
Oliveira, Vanessa G.
Fonseca, João Eurico
Graca, Luis
author_role author
author2 Agua-Doce, Ana
Oliveira, Vanessa G.
Fonseca, João Eurico
Graca, Luis
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Duarte, Joana
Agua-Doce, Ana
Oliveira, Vanessa G.
Fonseca, João Eurico
Graca, Luis
dc.subject.por.fl_str_mv Rheumatoid arthritis
Th 17
Treg cells
Foxp3
Antigens, CD4
topic Rheumatoid arthritis
Th 17
Treg cells
Foxp3
Antigens, CD4
description ©2010 Duarte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
publishDate 2010
dc.date.none.fl_str_mv 2010-05
2010-05-01T00:00:00Z
2012-04-18T16:02:44Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/6033
url http://hdl.handle.net/10451/6033
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS ONE | May 2010 | Volume 5 | Issue 5 | e10558
1932-6203
10.1371/journal.pone.0010558
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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