Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus

Detalhes bibliográficos
Autor(a) principal: Caramalho, I.
Data de Publicação: 2014
Outros Autores: Nunes-Silva, V., Pires, A. R., Mota, C., Pinto, A. I., Nunes-Cabaço, H., Foxall, R. B., Sousa, A. E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/18438
Resumo: © 2014 Elsevier Ltd. All rights reserved.
id RCAP_680fb70be36dcc298595f194389cdfe5
oai_identifier_str oai:repositorio.ul.pt:10451/18438
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymusCommon gamma-chain cytokinesRegulatory T cellsImmune toleranceFOXP3Human T-cell development© 2014 Elsevier Ltd. All rights reserved.Thymus-derived FOXP3-expressing regulatory T-cells (tTregs) are master orchestrators of physiological and pathological immune responses, thus constituting ideal targets for the treatment of autoimmunity. Despite their clinical importance, the developmental program governing their differentiation in the human thymus remains poorly understood. Here, we investigated the role of common gamma-chain cytokines in human tTreg differentiation, by performing gain- and loss-of-function experiments in 3D and 2D postnatal thymic cultures. We identified IL-2 and IL-15 as key molecular determinants in this process and excluded a major function for IL-4, IL-7 and IL-21. Mechanistically, IL-2 and IL-15 were equally able to drive tTreg precursor differentiation into FOXP3(+) cells, and promote tTreg proliferation and survival. Both cytokines also increased the expression levels of molecules associated with effector function within FOXP3(+) subsets, supporting their involvement in tTreg functional maturation. Furthermore, we revealed that IL-2 and IL-15 are expressed in a non-overlapping pattern in the human thymus, with the former produced mainly by mature αβ and γδ thymocytes and the latter by monocyte/macrophages and B lymphocytes. Our results identify core mechanisms dictating human tTreg development, with IL-2 and IL-15 defining specific niches required for tTreg lineage stabilization and differentiation, with implications for their therapeutic targeting in autoimmune conditions.This work was supported by Fundação para a Ciência e a Tecnologia, under Grant PTDC/SAU-IMU/113541/2009 (to IC).ElsevierRepositório da Universidade de LisboaCaramalho, I.Nunes-Silva, V.Pires, A. R.Mota, C.Pinto, A. I.Nunes-Cabaço, H.Foxall, R. B.Sousa, A. E.2015-07-14T11:01:27Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/18438engJournal of Autoimmunity 56 (2015) 98e1100896-8411http://dx.doi.org/10.1016/j.jaut.2014.11.002metadata 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:RCAAP2023-11-08T16:04:33Zoai:repositorio.ul.pt:10451/18438Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:37:54.707746Repositório 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 Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
title Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
spellingShingle Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
Caramalho, I.
Common gamma-chain cytokines
Regulatory T cells
Immune tolerance
FOXP3
Human T-cell development
title_short Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
title_full Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
title_fullStr Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
title_full_unstemmed Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
title_sort Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
author Caramalho, I.
author_facet Caramalho, I.
Nunes-Silva, V.
Pires, A. R.
Mota, C.
Pinto, A. I.
Nunes-Cabaço, H.
Foxall, R. B.
Sousa, A. E.
author_role author
author2 Nunes-Silva, V.
Pires, A. R.
Mota, C.
Pinto, A. I.
Nunes-Cabaço, H.
Foxall, R. B.
Sousa, A. E.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Caramalho, I.
Nunes-Silva, V.
Pires, A. R.
Mota, C.
Pinto, A. I.
Nunes-Cabaço, H.
Foxall, R. B.
Sousa, A. E.
dc.subject.por.fl_str_mv Common gamma-chain cytokines
Regulatory T cells
Immune tolerance
FOXP3
Human T-cell development
topic Common gamma-chain cytokines
Regulatory T cells
Immune tolerance
FOXP3
Human T-cell development
description © 2014 Elsevier Ltd. All rights reserved.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
2015-07-14T11:01:27Z
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/10451/18438
url http://hdl.handle.net/10451/18438
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Autoimmunity 56 (2015) 98e110
0896-8411
http://dx.doi.org/10.1016/j.jaut.2014.11.002
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 Elsevier
publisher.none.fl_str_mv Elsevier
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
repository.mail.fl_str_mv
_version_ 1799134277541036032

Registros relacionados