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WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells
A large proportion of Wiskott-Aldrich syndrome (WAS) patients develop autoimmunity and allergy. CD4(+)CD25(+)FOXP3(+) natural regulatory T (nTreg) cells play a key role in peripheral tolerance to prevent immune responses to self-antigens and allergens. Therefore, we investigated the effect of WAS pr...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118740/ https://www.ncbi.nlm.nih.gov/pubmed/17296785 http://dx.doi.org/10.1084/jem.20061334 |
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author | Marangoni, Francesco Trifari, Sara Scaramuzza, Samantha Panaroni, Cristina Martino, Silvana Notarangelo, Luigi D. Baz, Zeina Metin, Ayse Cattaneo, Federica Villa, Anna Aiuti, Alessandro Battaglia, Manuela Roncarolo, Maria-Grazia Dupré, Loïc |
author_facet | Marangoni, Francesco Trifari, Sara Scaramuzza, Samantha Panaroni, Cristina Martino, Silvana Notarangelo, Luigi D. Baz, Zeina Metin, Ayse Cattaneo, Federica Villa, Anna Aiuti, Alessandro Battaglia, Manuela Roncarolo, Maria-Grazia Dupré, Loïc |
author_sort | Marangoni, Francesco |
collection | PubMed |
description | A large proportion of Wiskott-Aldrich syndrome (WAS) patients develop autoimmunity and allergy. CD4(+)CD25(+)FOXP3(+) natural regulatory T (nTreg) cells play a key role in peripheral tolerance to prevent immune responses to self-antigens and allergens. Therefore, we investigated the effect of WAS protein (WASP) deficiency on the distribution and suppressor function of nTreg cells. In WAS(−/−) mice, the steady-state distribution and phenotype of nTreg cells in the thymus and spleen were normal. However, WAS(−/−) nTreg cells engrafted poorly in immunized mice, indicating perturbed homeostasis. Moreover, WAS(−/−) nTreg cells failed to proliferate and to produce transforming growth factor β upon T cell receptor (TCR)/CD28 triggering. WASP-dependent F-actin polarization to the site of TCR triggering might not be involved in WAS(−/−) nTreg cell defects because this process was also inefficient in wild-type (WT) nTreg cells. Compared with WT nTreg cells, WAS(−/−) nTreg cells showed reduced in vitro suppressor activity on both WT and WAS(−/−) effector T cells. Similarly, peripheral nTreg cells were present at normal levels in WAS patients but failed to suppress proliferation of autologous and allogeneic CD4(+) effector T cells in vitro. Thus, WASP appears to play an important role in the activation and suppressor function of nTreg cells, and a dysfunction or incorrect localization of nTreg cells may contribute to the development of autoimmunity in WAS patients. |
format | Text |
id | pubmed-2118740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21187402007-12-13 WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells Marangoni, Francesco Trifari, Sara Scaramuzza, Samantha Panaroni, Cristina Martino, Silvana Notarangelo, Luigi D. Baz, Zeina Metin, Ayse Cattaneo, Federica Villa, Anna Aiuti, Alessandro Battaglia, Manuela Roncarolo, Maria-Grazia Dupré, Loïc J Exp Med Articles A large proportion of Wiskott-Aldrich syndrome (WAS) patients develop autoimmunity and allergy. CD4(+)CD25(+)FOXP3(+) natural regulatory T (nTreg) cells play a key role in peripheral tolerance to prevent immune responses to self-antigens and allergens. Therefore, we investigated the effect of WAS protein (WASP) deficiency on the distribution and suppressor function of nTreg cells. In WAS(−/−) mice, the steady-state distribution and phenotype of nTreg cells in the thymus and spleen were normal. However, WAS(−/−) nTreg cells engrafted poorly in immunized mice, indicating perturbed homeostasis. Moreover, WAS(−/−) nTreg cells failed to proliferate and to produce transforming growth factor β upon T cell receptor (TCR)/CD28 triggering. WASP-dependent F-actin polarization to the site of TCR triggering might not be involved in WAS(−/−) nTreg cell defects because this process was also inefficient in wild-type (WT) nTreg cells. Compared with WT nTreg cells, WAS(−/−) nTreg cells showed reduced in vitro suppressor activity on both WT and WAS(−/−) effector T cells. Similarly, peripheral nTreg cells were present at normal levels in WAS patients but failed to suppress proliferation of autologous and allogeneic CD4(+) effector T cells in vitro. Thus, WASP appears to play an important role in the activation and suppressor function of nTreg cells, and a dysfunction or incorrect localization of nTreg cells may contribute to the development of autoimmunity in WAS patients. The Rockefeller University Press 2007-02-19 /pmc/articles/PMC2118740/ /pubmed/17296785 http://dx.doi.org/10.1084/jem.20061334 Text en Copyright © 2007, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Marangoni, Francesco Trifari, Sara Scaramuzza, Samantha Panaroni, Cristina Martino, Silvana Notarangelo, Luigi D. Baz, Zeina Metin, Ayse Cattaneo, Federica Villa, Anna Aiuti, Alessandro Battaglia, Manuela Roncarolo, Maria-Grazia Dupré, Loïc WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells |
title | WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells |
title_full | WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells |
title_fullStr | WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells |
title_full_unstemmed | WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells |
title_short | WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells |
title_sort | wasp regulates suppressor activity of human and murine cd4(+)cd25(+)foxp3(+) natural regulatory t cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118740/ https://www.ncbi.nlm.nih.gov/pubmed/17296785 http://dx.doi.org/10.1084/jem.20061334 |
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