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The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development
CD4(+) regulatory T cells (T(reg) cells) expressing the transcription factor Foxp3 play a pivotal role in maintaining peripheral tolerance by inhibiting the expansion and function of pathogenic conventional T cells (T(conv) cells). In this study, we show that a locus on rat chromosome 9 controls the...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201202/ https://www.ncbi.nlm.nih.gov/pubmed/21948080 http://dx.doi.org/10.1084/jem.20102191 |
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author | Colacios, Céline Casemayou, Audrey Dejean, Anne S. Gaits-Iacovoni, Frédérique Pedros, Christophe Bernard, Isabelle Lagrange, Dominique Deckert, Marcel Lamouroux, Lucille Jagodic, Maja Olsson, Tomas Liblau, Roland S. Fournié, Gilbert J. Saoudi, Abdelhadi |
author_facet | Colacios, Céline Casemayou, Audrey Dejean, Anne S. Gaits-Iacovoni, Frédérique Pedros, Christophe Bernard, Isabelle Lagrange, Dominique Deckert, Marcel Lamouroux, Lucille Jagodic, Maja Olsson, Tomas Liblau, Roland S. Fournié, Gilbert J. Saoudi, Abdelhadi |
author_sort | Colacios, Céline |
collection | PubMed |
description | CD4(+) regulatory T cells (T(reg) cells) expressing the transcription factor Foxp3 play a pivotal role in maintaining peripheral tolerance by inhibiting the expansion and function of pathogenic conventional T cells (T(conv) cells). In this study, we show that a locus on rat chromosome 9 controls the size of the natural T(reg) cell compartment. Fine mapping of this locus with interval-specific congenic lines and association experiments using single nucleotide polymorphisms (SNPs) identified a nonsynonymous SNP in the Vav1 gene that leads to the substitution of an arginine by a tryptophan (p.Arg63Trp). This p.Arg63Trp polymorphism is associated with increased proportion and absolute numbers of T(reg) cells in the thymus and peripheral lymphoid organs, without impacting the size of the T(conv) cell compartment. This polymorphism is also responsible for Vav1 constitutive activation, revealed by its tyrosine 174 hyperphosphorylation and increased guanine nucleotide exchange factor activity. Moreover, it induces a marked reduction in Vav1 cellular contents and a reduction of Ca(2+) flux after TCR engagement. Together, our data reveal a key role for Vav1-dependent T cell antigen receptor signaling in natural T(reg) cell development. |
format | Online Article Text |
id | pubmed-3201202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32012022012-04-24 The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development Colacios, Céline Casemayou, Audrey Dejean, Anne S. Gaits-Iacovoni, Frédérique Pedros, Christophe Bernard, Isabelle Lagrange, Dominique Deckert, Marcel Lamouroux, Lucille Jagodic, Maja Olsson, Tomas Liblau, Roland S. Fournié, Gilbert J. Saoudi, Abdelhadi J Exp Med Brief Definitive Report CD4(+) regulatory T cells (T(reg) cells) expressing the transcription factor Foxp3 play a pivotal role in maintaining peripheral tolerance by inhibiting the expansion and function of pathogenic conventional T cells (T(conv) cells). In this study, we show that a locus on rat chromosome 9 controls the size of the natural T(reg) cell compartment. Fine mapping of this locus with interval-specific congenic lines and association experiments using single nucleotide polymorphisms (SNPs) identified a nonsynonymous SNP in the Vav1 gene that leads to the substitution of an arginine by a tryptophan (p.Arg63Trp). This p.Arg63Trp polymorphism is associated with increased proportion and absolute numbers of T(reg) cells in the thymus and peripheral lymphoid organs, without impacting the size of the T(conv) cell compartment. This polymorphism is also responsible for Vav1 constitutive activation, revealed by its tyrosine 174 hyperphosphorylation and increased guanine nucleotide exchange factor activity. Moreover, it induces a marked reduction in Vav1 cellular contents and a reduction of Ca(2+) flux after TCR engagement. Together, our data reveal a key role for Vav1-dependent T cell antigen receptor signaling in natural T(reg) cell development. The Rockefeller University Press 2011-10-24 /pmc/articles/PMC3201202/ /pubmed/21948080 http://dx.doi.org/10.1084/jem.20102191 Text en © 2011 Colacios et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Colacios, Céline Casemayou, Audrey Dejean, Anne S. Gaits-Iacovoni, Frédérique Pedros, Christophe Bernard, Isabelle Lagrange, Dominique Deckert, Marcel Lamouroux, Lucille Jagodic, Maja Olsson, Tomas Liblau, Roland S. Fournié, Gilbert J. Saoudi, Abdelhadi The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development |
title | The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development |
title_full | The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development |
title_fullStr | The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development |
title_full_unstemmed | The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development |
title_short | The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development |
title_sort | p.arg63trp polymorphism controls vav1 functions and foxp3 regulatory t cell development |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201202/ https://www.ncbi.nlm.nih.gov/pubmed/21948080 http://dx.doi.org/10.1084/jem.20102191 |
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