The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function

Michela Locci, Elena Dra Ghici, Francesco Marangoni, Marita Bosticardo, Marco Catucci, Alessandro Aiuti, Caterina Cancrini, Laszlo Marodi, Teresa Espanol, Robbert G M Bredius, Adrian J. Thrasher, Ansgar Schulz, Jiri Litzman, Maria Grazia Roncarolo, Giulia Casorati, Paolo Dellabona, Anna Villa

Research output: Contribution to journalArticle

Abstract

The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was-/- mice. iNKT cell numbers were signifcantly reduced in the thymus and periphery of was-/- mice as compared with wild-type controls. Moreover analysis of was-/- iNKT cell maturation revealed a complete arrest at the CD44+ NK1.1- intermediate stage. Notably, generation of BM chimeras demonstrated a was -/- iNKT cell-autonomous developmental defect. was-/- iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon γ upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology.

Original languageEnglish
Pages (from-to)735-742
Number of pages8
JournalJournal of Experimental Medicine
Volume206
Issue number4
DOIs
Publication statusPublished - Apr 13 2009

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Wiskott-Aldrich Syndrome Protein
Natural Killer T-Cells
Wiskott-Aldrich Syndrome
Proteins
Actin Cytoskeleton
Interleukin-4
Thymus Gland
Interferons
Cell Count
Pathology

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function. / Locci, Michela; Ghici, Elena Dra; Marangoni, Francesco; Bosticardo, Marita; Catucci, Marco; Aiuti, Alessandro; Cancrini, Caterina; Marodi, Laszlo; Espanol, Teresa; Bredius, Robbert G M; Thrasher, Adrian J.; Schulz, Ansgar; Litzman, Jiri; Roncarolo, Maria Grazia; Casorati, Giulia; Dellabona, Paolo; Villa, Anna.

In: Journal of Experimental Medicine, Vol. 206, No. 4, 13.04.2009, p. 735-742.

Research output: Contribution to journalArticle

Locci, M, Ghici, ED, Marangoni, F, Bosticardo, M, Catucci, M, Aiuti, A, Cancrini, C, Marodi, L, Espanol, T, Bredius, RGM, Thrasher, AJ, Schulz, A, Litzman, J, Roncarolo, MG, Casorati, G, Dellabona, P & Villa, A 2009, 'The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function', Journal of Experimental Medicine, vol. 206, no. 4, pp. 735-742. https://doi.org/10.1084/jem.20081773
Locci, Michela ; Ghici, Elena Dra ; Marangoni, Francesco ; Bosticardo, Marita ; Catucci, Marco ; Aiuti, Alessandro ; Cancrini, Caterina ; Marodi, Laszlo ; Espanol, Teresa ; Bredius, Robbert G M ; Thrasher, Adrian J. ; Schulz, Ansgar ; Litzman, Jiri ; Roncarolo, Maria Grazia ; Casorati, Giulia ; Dellabona, Paolo ; Villa, Anna. / The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 4. pp. 735-742.
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