WASP regulates suppressor activity of human and murine CD4 +CD25+FOXP3+ natural regulatory T cells

Francesco Marangoni, Sara Trifari, Samantha Scaramuzza, Cristina Panaroni, Silvana Martino, Luigi D. Notarangelo, Zeina Baz, Ayse Metin, Federica Cattaneo, Anna Villa, Alessandro Aiuti, Manuela Battaglia, Maria Grazia Roncarolo, Loïc Dupré

Research output: Contribution to journalArticle

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Abstract

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. JEM

Original languageEnglish
Pages (from-to)369-380
Number of pages12
JournalJournal of Experimental Medicine
Volume204
Issue number2
DOIs
Publication statusPublished - Feb 2007

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Wiskott-Aldrich Syndrome
Regulatory T-Lymphocytes
Human Activities
Proteins
T-Cell Antigen Receptor
Autoimmunity
Wiskott-Aldrich Syndrome Protein
Peripheral Tolerance
T-Lymphocytes
Protein Deficiency
Autoantigens
Transforming Growth Factors
Allergens
Thymus Gland
Actins
Hypersensitivity
Homeostasis
Spleen
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

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.

In: Journal of Experimental Medicine, Vol. 204, No. 2, 02.2007, p. 369-380.

Research output: Contribution to journalArticle

Marangoni, F, Trifari, S, Scaramuzza, S, Panaroni, C, Martino, S, Notarangelo, LD, Baz, Z, Metin, A, Cattaneo, F, Villa, A, Aiuti, A, Battaglia, M, Roncarolo, MG & Dupré, L 2007, 'WASP regulates suppressor activity of human and murine CD4 +CD25+FOXP3+ natural regulatory T cells', Journal of Experimental Medicine, vol. 204, no. 2, pp. 369-380. https://doi.org/10.1084/jem.20061334
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. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 2. pp. 369-380.
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