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J Immunol. 2007 Apr 1;178(7):4153-8.

Gadd45alpha regulates p38-dependent dendritic cell cytokine production and Th1 differentiation.

Author information

1
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Gadd45alpha inhibits the activation of p38 by the T cell alternative pathway involving phosphorylation of p38 Tyr(323). Given that T cell p38 may play a role in Th1 development, the response to Th-skewing Ags was analyzed in Gadd45alpha(-/-) mice. Despite constitutively increased p38 activity in Gadd45alpha(-/-) T cells, the Th1 immune response to Toxoplasma gondii Ag (STAg), was diminished. In contrast to T cells, dendritic cells (DC) lacked the alternative p38 activation pathway. Gadd45alpha(-/-) DCs responded to STAg with low levels of MAP kinase cascade-dependent p38 activation, IL-12 production, and CD40 expression. Wild-type T cells transferred into Gadd45alpha(-/-) recipients had a diminished Th1 response to STAg, whereas Gadd45alpha(-/-) T cells transferred into wild-type hosts behaved normally. Therefore, Gadd45alpha has tissue-specific and opposing functions on p38 activity, and Gadd45alpha-regulated p38 activation in DCs is a critical event in Th1 polarization in vivo.

PMID:
17371971
DOI:
10.4049/jimmunol.178.7.4153
[Indexed for MEDLINE]
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