Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/900 |
Resumo: | Abstract The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo. |
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Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cellsAbstract The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo.The Laboratory of Human Genetics of Infectious Diseases is supported by the Agence Nationale de la Recherche, the Programme Hospitalier de Recherche Clinique, the European Union (grant LHSP-CT-2005-018736), the BNP Paribas Foundation, the March of Dimes, the Dana Foundation, and the Candi’Oser Association. L. de Beaucoudrey is supported by the Fondation pour la Recherche Medicale as part of the PhD program of Pierre et Marie Curie University. J.L. Casanova is an International Scholar of the Howard Hughes Medical Institute.Rockefeller University PressRepositório Científico do Centro Hospitalar Universitário de Santo AntónioBeaucoudrey, L.Puel, A.Filipe-Santos, O.Cobat, A.Ghandil, P.Chrabieh, M.Feinberg, J.Bernuth, H.Samarina, A.Jannière, L.Fieschi, C.Stéphan, J.Boileau, C.Lyonnet, S.Jondeau, G.Cormier-Daire, V.Merrer, M.Hoarau, C.Lebranchu, Y.Lortholary, O.Chandesris, M.Tron, F.Gambineri, E.Bianchi, L.Rodriguez-Gallego, C.Zitnik, S.Vasconcelos, J.Guedes, M.Vitor, A.Marodi, L.Chapel, H.Reid, B.Roifman, C.Nadal, D.Reichenbach, J.Caragol, I.Garty, B.Dogu, F.Camcioglu, Y.Gülle, S.Sanal, O.Fischer, A.Abel, L.Stockinger, B.Picard, C.Casanova, J.2012-03-26T11:17:28Z2008-072008-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/900engJ Exp Med. 2008 Jul 7;205(7):1543-500022-1007info: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:RCAAP2023-10-20T10:54:19Zoai:repositorio.chporto.pt:10400.16/900Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:37:30.473431Repositório 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 |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells |
title |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells |
spellingShingle |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells Beaucoudrey, L. |
title_short |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells |
title_full |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells |
title_fullStr |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells |
title_full_unstemmed |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells |
title_sort |
Mutations in STAT3 and IL12RB1 impair the development of human IL-17 – producing T cells |
author |
Beaucoudrey, L. |
author_facet |
Beaucoudrey, L. Puel, A. Filipe-Santos, O. Cobat, A. Ghandil, P. Chrabieh, M. Feinberg, J. Bernuth, H. Samarina, A. Jannière, L. Fieschi, C. Stéphan, J. Boileau, C. Lyonnet, S. Jondeau, G. Cormier-Daire, V. Merrer, M. Hoarau, C. Lebranchu, Y. Lortholary, O. Chandesris, M. Tron, F. Gambineri, E. Bianchi, L. Rodriguez-Gallego, C. Zitnik, S. Vasconcelos, J. Guedes, M. Vitor, A. Marodi, L. Chapel, H. Reid, B. Roifman, C. Nadal, D. Reichenbach, J. Caragol, I. Garty, B. Dogu, F. Camcioglu, Y. Gülle, S. Sanal, O. Fischer, A. Abel, L. Stockinger, B. Picard, C. Casanova, J. |
author_role |
author |
author2 |
Puel, A. Filipe-Santos, O. Cobat, A. Ghandil, P. Chrabieh, M. Feinberg, J. Bernuth, H. Samarina, A. Jannière, L. Fieschi, C. Stéphan, J. Boileau, C. Lyonnet, S. Jondeau, G. Cormier-Daire, V. Merrer, M. Hoarau, C. Lebranchu, Y. Lortholary, O. Chandesris, M. Tron, F. Gambineri, E. Bianchi, L. Rodriguez-Gallego, C. Zitnik, S. Vasconcelos, J. Guedes, M. Vitor, A. Marodi, L. Chapel, H. Reid, B. Roifman, C. Nadal, D. Reichenbach, J. Caragol, I. Garty, B. Dogu, F. Camcioglu, Y. Gülle, S. Sanal, O. Fischer, A. Abel, L. Stockinger, B. Picard, C. Casanova, J. |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Beaucoudrey, L. Puel, A. Filipe-Santos, O. Cobat, A. Ghandil, P. Chrabieh, M. Feinberg, J. Bernuth, H. Samarina, A. Jannière, L. Fieschi, C. Stéphan, J. Boileau, C. Lyonnet, S. Jondeau, G. Cormier-Daire, V. Merrer, M. Hoarau, C. Lebranchu, Y. Lortholary, O. Chandesris, M. Tron, F. Gambineri, E. Bianchi, L. Rodriguez-Gallego, C. Zitnik, S. Vasconcelos, J. Guedes, M. Vitor, A. Marodi, L. Chapel, H. Reid, B. Roifman, C. Nadal, D. Reichenbach, J. Caragol, I. Garty, B. Dogu, F. Camcioglu, Y. Gülle, S. Sanal, O. Fischer, A. Abel, L. Stockinger, B. Picard, C. Casanova, J. |
description |
Abstract The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-07 2008-07-01T00:00:00Z 2012-03-26T11:17:28Z |
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/10400.16/900 |
url |
http://hdl.handle.net/10400.16/900 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
J Exp Med. 2008 Jul 7;205(7):1543-50 0022-1007 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Rockefeller University Press |
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Rockefeller University Press |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133636954423296 |