Development of central nervous system autoimmunity is impaired in the absence of wiskott-aldrich syndrome protein

Marita Bosticardo, Silvia Musio, Elena Fontana, Stefano Angiari, Elena Draghici, Gabriela Constantin, Pietro L. Poliani, Rosetta Pedotti, Anna Villa

Research output: Contribution to journalArticle

Abstract

Wiskott-Aldrich Syndrome protein (WASP) is a key regulator of the actin cytoskeleton in hematopoietic cells. Defective expression of WASP leads to multiple abnormalities in different hematopoietic cells. Despite severe impairment of T cell function, WAS patients exhibit a high prevalence of autoimmune disorders. We attempted to induce EAE, an animal model of organ-specific autoimmunity affecting the CNS that mimics human MS, in Was -/- mice. We describe here that Was-/- mice are markedly resistant against EAE, showing lower incidence and milder score, reduced CNS inflammation and demyelination as compared to WT mice. Microglia was only poorly activated in Was-/- mice. Antigen-induced T-cell proliferation, Th-1 and -17 cytokine production and integrin-dependent adhesion were increased in Was-/- mice. However, adoptive transfer of MOG-activated T cells from Was-/- mice in WT mice failed to induce EAE. Was-/- mice were resistant against EAE also when induced by adoptive transfer of MOG-activated T cells from WT mice. Was+/- heterozygous mice developed an intermediate clinical phenotype between WT and Was-/- mice, and they displayed a mixed population of WASP-positive and -negative T cells in the periphery but not in their CNS parenchyma, where the large majority of inflammatory cells expressed WASP. In conclusion, in absence of WASP, T-cell responses against a CNS autoantigen are increased, but the ability of autoreactive T cells to induce CNS autoimmunity is impaired, most probably because of an inefficient T-cell transmigration into the CNS and defective CNS resident microglial function.

Original languageEnglish
Article numbere86942
JournalPLoS One
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 23 2014

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Wiskott-Aldrich Syndrome Protein
autoimmunity
neurodevelopment
T-cells
Neurology
Autoimmunity
Central Nervous System
T-lymphocytes
mice
T-Lymphocytes
proteins
Adoptive Transfer
Autoantigens
Cell proliferation
autoantigens
Multiple Abnormalities
Animal Structures
Integrins
Actins
Animals

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Development of central nervous system autoimmunity is impaired in the absence of wiskott-aldrich syndrome protein. / Bosticardo, Marita; Musio, Silvia; Fontana, Elena; Angiari, Stefano; Draghici, Elena; Constantin, Gabriela; Poliani, Pietro L.; Pedotti, Rosetta; Villa, Anna.

In: PLoS One, Vol. 9, No. 1, e86942, 23.01.2014.

Research output: Contribution to journalArticle

Bosticardo, M, Musio, S, Fontana, E, Angiari, S, Draghici, E, Constantin, G, Poliani, PL, Pedotti, R & Villa, A 2014, 'Development of central nervous system autoimmunity is impaired in the absence of wiskott-aldrich syndrome protein', PLoS One, vol. 9, no. 1, e86942. https://doi.org/10.1371/journal.pone.0086942
Bosticardo, Marita ; Musio, Silvia ; Fontana, Elena ; Angiari, Stefano ; Draghici, Elena ; Constantin, Gabriela ; Poliani, Pietro L. ; Pedotti, Rosetta ; Villa, Anna. / Development of central nervous system autoimmunity is impaired in the absence of wiskott-aldrich syndrome protein. In: PLoS One. 2014 ; Vol. 9, No. 1.
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