Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development

Detalhes bibliográficos
Autor(a) principal: Almeida, Vinicius Cotta de
Data de Publicação: 2007
Outros Autores: Westerberg, Lisa, Maillard, Michel H., Onaldi, Dilek, Wachtel, Heather, Meelu, Parool, Chung, Ung-il, Xavier, Ramnik, Alt, Frederick W., Snapper, Scott B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/41081
Resumo: Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Massachusetts General Hospital. Center for the Study of Inflammatory Bowel Disease. Harvard Medical School. Department of Genetic. Boston, USA / Fundação Oswlaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
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spelling Almeida, Vinicius Cotta deWesterberg, LisaMaillard, Michel H.Onaldi, DilekWachtel, HeatherMeelu, ParoolChung, Ung-ilXavier, RamnikAlt, Frederick W.Snapper, Scott B.2020-05-04T17:34:03Z2020-05-04T17:34:03Z2007ALMEIDA, Vinicius Cotta de et al. Wiskott–Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. Proceedings of the National Academy of Sciences (PNAS), v. 104, n. 39, p. 1-6, Sept. 2007.0027-8424https://www.arca.fiocruz.br/handle/icict/4108110.1073/pnas.07068811041091-6490engNational Academy of SciencesCitoesqueletoTimoMigraçãoColiteRatos nocauteadosCytoskeletonThymusMigrationColitisKnockout miceWiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell developmentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleMassachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Massachusetts General Hospital. Center for the Study of Inflammatory Bowel Disease. Harvard Medical School. Department of Genetic. Boston, USA / Fundação Oswlaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Harvard Medical School. Department of Genetics. Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Harvard Medical School. Department of Genetics. Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Harvard Medical School. Department of Genetics. Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Massachusetts General Hospital. Endocrine Unit. Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Harvard Medical School. Department of Genetics. Boston, MA, USA.Massachusetts General Hospital. Endocrine Unit. Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Massachusetts General Hospital. Center for the Study of Inflammatory Bowel Disease. Harvard Medical School. Department of Genetic. Boston, USA / Massachusetts General Hospital. Department of Molecular Biology. Boston, MA, USA.Howard Hughes Medical Institute. Children’s Hospital. Boston, MA, USA / Center for Blood Research, Boston, MA, USA / Harvard Medical School. Department of Genetics. Boston, MA / USA / Fundação OSwaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Massachusetts General Hospital. Center for the Study of Inflammatory Bowel Disease. Harvard Medical School. Department of Genetic. Boston, USA / Fundação Oswlaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Although T cell dysfunction and lymphopenia are key features of immunodeficient patients with the Wiskott-Aldrich syndrome and Wiskott-Aldrich syndrome protein (WASP)-deficient mice, T cell development appears relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homologue of WASP, may serve a redundant function with WASP. To examine the unique and redundant activities of WASP and N-WASP, we generated ES cells devoid of WASP and N-WASP [double knockout (DKO)] and used the RAG-2-deficient blastocyst complementation system to generate DKO lymphocytes. Moreover, we mated WASP KO mice with mice containing a conditionally targeted N-WASP allele and used the Cre-loxP system to generate mice lacking WASP and N-WASP in T cells [conditional DKO (cDKO)]. In both systems, N-WASP-deficient cells were indistinguishable from WT cells. In contrast, T cell development in DKO and cDKO mice was markedly altered, as shown by thymic hypocellularity and reduced numbers of peripheral T cells. We found that the combined activity of WASP and N-WASP was important for CD4(-)CD8(-) double-negative (DN)-to-CD4(+)CD8(+) double-positive (DP) cell transition, and this may be partly explained by reduced cycling DN3 cells. In addition, decreased migratory responses of CD4(+)CD8(-) and CD4(-)CD8(+) single-positive (SP) cells and increased percentage of CD69(low)CD24(low) and CD62L(low) SP cells in cDKO cells imply retention of SP cells in the thymus. In summary, this study suggests that, although WASP serves a unique role for peripheral T cell function, T cell development depends on the combined activity of WASP and N-WASP.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/41081/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALRamnikXavier_ViniusCAlmeida_etal_IOC_2007.pdfRamnikXavier_ViniusCAlmeida_etal_IOC_2007.pdfapplication/pdf1272127https://www.arca.fiocruz.br/bitstream/icict/41081/2/RamnikXavier_ViniusCAlmeida_etal_IOC_2007.pdf4bb03dc6f088f10f6c35fbb754288addMD52TEXTRamnikXavier_ViniusCAlmeida_etal_IOC_2007.pdf.txtRamnikXavier_ViniusCAlmeida_etal_IOC_2007.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
title Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
spellingShingle Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
Almeida, Vinicius Cotta de
Citoesqueleto
Timo
Migração
Colite
Ratos nocauteados
Cytoskeleton
Thymus
Migration
Colitis
Knockout mice
title_short Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
title_full Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
title_fullStr Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
title_full_unstemmed Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
title_sort Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development
author Almeida, Vinicius Cotta de
author_facet Almeida, Vinicius Cotta de
Westerberg, Lisa
Maillard, Michel H.
Onaldi, Dilek
Wachtel, Heather
Meelu, Parool
Chung, Ung-il
Xavier, Ramnik
Alt, Frederick W.
Snapper, Scott B.
author_role author
author2 Westerberg, Lisa
Maillard, Michel H.
Onaldi, Dilek
Wachtel, Heather
Meelu, Parool
Chung, Ung-il
Xavier, Ramnik
Alt, Frederick W.
Snapper, Scott B.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Almeida, Vinicius Cotta de
Westerberg, Lisa
Maillard, Michel H.
Onaldi, Dilek
Wachtel, Heather
Meelu, Parool
Chung, Ung-il
Xavier, Ramnik
Alt, Frederick W.
Snapper, Scott B.
dc.subject.other.pt_BR.fl_str_mv Citoesqueleto
Timo
Migração
Colite
Ratos nocauteados
topic Citoesqueleto
Timo
Migração
Colite
Ratos nocauteados
Cytoskeleton
Thymus
Migration
Colitis
Knockout mice
dc.subject.en.pt_BR.fl_str_mv Cytoskeleton
Thymus
Migration
Colitis
Knockout mice
description Massachusetts General Hospital. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Massachusetts General Hospital. Center for the Study of Inflammatory Bowel Disease. Harvard Medical School. Department of Genetic. Boston, USA / Fundação Oswlaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
publishDate 2007
dc.date.issued.fl_str_mv 2007
dc.date.accessioned.fl_str_mv 2020-05-04T17:34:03Z
dc.date.available.fl_str_mv 2020-05-04T17:34:03Z
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.citation.fl_str_mv ALMEIDA, Vinicius Cotta de et al. Wiskott–Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. Proceedings of the National Academy of Sciences (PNAS), v. 104, n. 39, p. 1-6, Sept. 2007.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/41081
dc.identifier.issn.pt_BR.fl_str_mv 0027-8424
dc.identifier.doi.none.fl_str_mv 10.1073/pnas.0706881104
dc.identifier.eissn.none.fl_str_mv 1091-6490
identifier_str_mv ALMEIDA, Vinicius Cotta de et al. Wiskott–Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. Proceedings of the National Academy of Sciences (PNAS), v. 104, n. 39, p. 1-6, Sept. 2007.
0027-8424
10.1073/pnas.0706881104
1091-6490
url https://www.arca.fiocruz.br/handle/icict/41081
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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