Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells

Detalhes bibliográficos
Autor(a) principal: Mota, Catarina
Data de Publicação: 2014
Outros Autores: Nunes-Silva, Vânia, Pires, Ana R., Matoso, Paula, Victorino, Rui M. M., Sousa, Ana E., Caramalho, Íris
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/18441
Resumo: © 2014 by The American Association of Immunologists, Inc.
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spelling Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells© 2014 by The American Association of Immunologists, Inc.FOXP3-expressing regulatory T cells (Treg) are essential for the prevention of autoimmunity and were shown to be reduced and/or dysfunctional in several autoimmune diseases. Although Treg-based adoptive transfer represents a promising therapy, the large cell number required to achieve clinical efficacy constitutes an important limitation. Therefore, novel strategies to generate bona fide in vitro-induced Treg (iTreg) are critical. In this study, we report that human memory CD4 T cells can be efficiently converted into iTreg, and that Delta-like 1 (DL1)-mediated Notch signaling significantly enhances this process. The iTreg generated in the presence of DL1 featured higher levels of Treg function-associated molecules and were efficient suppressors. Importantly, these iTreg displayed a stable phenotype in long-term cultures, even in the presence of proinflammatory cytokines. Additionally, DL1 potentiated FOXP3 acquisition by memory CD4 cells through the modulation of the TGF-β signaling pathway and of Foxp3 transcription. Our data demonstrate that iTreg can be efficiently induced from memory CD4 cells, a subset enriched in relevant specificities for targeting in autoimmune diseases, and that DL1 enhances this process. DL1 also enhanced the proliferation and Treg function-associated marker expression of ex vivo-stimulated human circulating FOXP3(+) cells. Manipulation of the Notch signaling pathway constitutes a promising approach to boost the in vitro generation of iTreg and ex vivo Treg expansion, thus facilitating the establishment of effective Treg-based adoptive therapy in autoimmune diseases.This work was supported by Fundação para a Ciência e Tecnologia, Portugal Grant PTDC/SAU-IMU/113541/2009 (to I.C.) and Fellowship SFRH/SINTD/60059/2009 (to C.M.).The American Association of ImmunologistsRepositório da Universidade de LisboaMota, CatarinaNunes-Silva, VâniaPires, Ana R.Matoso, PaulaVictorino, Rui M. M.Sousa, Ana E.Caramalho, Íris2015-07-14T14:53:32Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/18441engJ Immunol 2014; 193:5854-58620022-1767http://dx.doi.org/ 10.4049/jimmunol.1400198metadata only accessinfo: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:RCAAP2023-11-08T16:04:32Zoai:repositorio.ul.pt:10451/18441Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:37:54.608020Repositório 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 Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
title Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
spellingShingle Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
Mota, Catarina
title_short Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
title_full Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
title_fullStr Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
title_full_unstemmed Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
title_sort Delta-like 1–mediated notch signaling enhances the in vitro conversion of human memory CD4 T cells into FOXP3-expressing regulatory T cells
author Mota, Catarina
author_facet Mota, Catarina
Nunes-Silva, Vânia
Pires, Ana R.
Matoso, Paula
Victorino, Rui M. M.
Sousa, Ana E.
Caramalho, Íris
author_role author
author2 Nunes-Silva, Vânia
Pires, Ana R.
Matoso, Paula
Victorino, Rui M. M.
Sousa, Ana E.
Caramalho, Íris
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Mota, Catarina
Nunes-Silva, Vânia
Pires, Ana R.
Matoso, Paula
Victorino, Rui M. M.
Sousa, Ana E.
Caramalho, Íris
description © 2014 by The American Association of Immunologists, Inc.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
2015-07-14T14:53:32Z
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/10451/18441
url http://hdl.handle.net/10451/18441
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Immunol 2014; 193:5854-5862
0022-1767
http://dx.doi.org/ 10.4049/jimmunol.1400198
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv The American Association of Immunologists
publisher.none.fl_str_mv The American Association of Immunologists
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
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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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