Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function

Vanessa Morales-Tirado, Dorothy K. Sojka, Shoshana D. Katzman, Christopher A. Lazarski, Fred D. Finkelman, Joseph F. Urban, Deborah J. Fowell

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Patients with Wiskott-Aldrich syndrome (WAS) have numerous immune cell deficiencies, but it remains unclear how abnormalities in individual cell types contribute to the pathologies of WAS. In T cells, the WAS protein (WASp) regulates actin polymerization and transcription, and plays a role in the dynamics of the immunologic synapse. To examine how these events influence CD4 function, we isolated theWASp deficiency to CD4+ T cells by adoptive transfer into wild-type mice to study T-cell priming and effector function. WAS-/- CD4+ T cells mediated protective T-helper 1 (Th1) responses to Leishmania major in vivo, but were unable to support Th2 immunity to Nippostrongylus brasiliensis or L major. Mechanistically, WASp was not required for Th2 programming but was required for Th2 effector function. WAS-/- CD4+ T cells up-regulated IL-4 and GATA3 mRNA and secreted IL-4 protein during Th2 differentiation. In contrast, cytokine transcription was uncoupled from protein production in WAS-/- Th2-primed effectors. WAS-/- Th2s failed to produce IL-4 protein on restimulation despite elevated IL-4/GATA3 mRNA. Moreover, dominant-negative WASp expression in WT effector T cells blocked IL-4 production, but had no effect on IFNγ. Thus WASp plays a selective, posttranscriptional role in Th2 effector function.

Original languageEnglish (US)
Pages (from-to)3498-3507
Number of pages10
JournalBlood
Volume115
Issue number17
DOIs
StatePublished - Apr 29 2010

Fingerprint

Wiskott-Aldrich Syndrome Protein
Wiskott-Aldrich Syndrome
T-cells
Interleukin-4
T-Lymphocytes
Proteins
Transcription
Nippostrongylus
Leishmania major
Messenger RNA
Adoptive Transfer
Pathology
Polymerization
Synapses
Actins
Immunity
Cytokines

All Science Journal Classification (ASJC) codes

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Morales-Tirado, V., Sojka, D. K., Katzman, S. D., Lazarski, C. A., Finkelman, F. D., Urban, J. F., & Fowell, D. J. (2010). Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function. Blood, 115(17), 3498-3507. https://doi.org/10.1182/blood-2009-07-235754

Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function. / Morales-Tirado, Vanessa; Sojka, Dorothy K.; Katzman, Shoshana D.; Lazarski, Christopher A.; Finkelman, Fred D.; Urban, Joseph F.; Fowell, Deborah J.

In: Blood, Vol. 115, No. 17, 29.04.2010, p. 3498-3507.

Research output: Contribution to journalArticle

Morales-Tirado, V, Sojka, DK, Katzman, SD, Lazarski, CA, Finkelman, FD, Urban, JF & Fowell, DJ 2010, 'Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function', Blood, vol. 115, no. 17, pp. 3498-3507. https://doi.org/10.1182/blood-2009-07-235754
Morales-Tirado V, Sojka DK, Katzman SD, Lazarski CA, Finkelman FD, Urban JF et al. Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function. Blood. 2010 Apr 29;115(17):3498-3507. https://doi.org/10.1182/blood-2009-07-235754
Morales-Tirado, Vanessa ; Sojka, Dorothy K. ; Katzman, Shoshana D. ; Lazarski, Christopher A. ; Finkelman, Fred D. ; Urban, Joseph F. ; Fowell, Deborah J. / Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function. In: Blood. 2010 ; Vol. 115, No. 17. pp. 3498-3507.
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