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Immunity. 2013 Jan 24;38(1):41-52. doi: 10.1016/j.immuni.2012.09.021. Epub 2013 Jan 3.

The kinase PKCα selectively upregulates interleukin-17A during Th17 cell immune responses.

Author information

1
Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria.

Abstract

Transforming growth-factor β (TGFβ) has been implicated in T helper 17 (Th17) cell biology and in triggering expression of interleukin-17A (IL-17A), which is a key Th17 cell cytokine. Deregulated TGFβ receptor (TGFβR) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGFβR pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C α (PKCα) as a signaling intermediate specific to the Th17 cell subset in the activation of TGFβRI. We have shown that PKCα physically interacts and functionally cooperates with TGFβRI to promote robust SMAD2-3 activation. Furthermore, PKCα-deficient (Prkca(-/-)) cells demonstrated a defect in SMAD-dependent IL-2 suppression, as well as decreased STAT3 DNA binding within the Il17a promoter. Consistently, Prkca(-/-) cells failed to mount appropriate IL-17A, but not IL-17F, responses in vitro and were resistant to induction of Th17-cell-dependent experimental autoimmune encephalomyelitis in vivo.

PMID:
23290522
PMCID:
PMC3556779
DOI:
10.1016/j.immuni.2012.09.021
[Indexed for MEDLINE]
Free PMC Article

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