Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1-deficient mice

Yoshihiko Tanaka, Takanori So, Svetlana Lebedeva, Michael Croft, Amnon Altman

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Although c-Maf is crucial for Th2 differentiation and production of interleukin 4 (IL-4), its regulation is poorly understood. We report that Vav1-/- CD4+ T cells display deficient T-cell receptor (TCR)/CD28-induced IL-4 and c-Maf expression and, conversely, enhanced interferon γ (IFN-γ) production and T-bet expression (even when cultured under Th2-polarizing conditions), but intact expression of other Th2 cytokines and GATA-3. Up-regulation of c-Maf was dependent on Ca 2+/nuclear factor of activated T cell (NFAT) and, together with IL-4 production, could be rescued in Vav1-/- T cells by Ca2+ ionophore. Deficient IL-4 production was restored by retrovirus-mediated Vav1 expression, but only partially by retroviral c-Maf expression. Similar IL-4 → IFN-γ skewing was observed in intact, antigen-primed Vav1 -/- mice. Thus, Vav1 is selectively required for IL-4 and c-Maf expression, a requirement reflecting, at least in part, the dependence of c-Maf expression on Ca2+/NFAT signaling.

Original languageEnglish
Pages (from-to)1286-1295
Number of pages10
JournalBlood
Volume106
Issue number4
DOIs
Publication statusPublished - 2005 Aug 15

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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