The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses

Marlies Meisel, Natascha Hermann-Kleiter, Reinhard Hinterleitner, Thomas Gruber, Katarzyna Wachowicz, Christa Pfeifhofer-Obermair, Friedrich Fresser, Michael Leitges, Cristiana Soldani, Antonella Viola, Sandra Kaminski, Gottfried Baier

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)41-52
Number of pages12
JournalImmunity
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 24 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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  • Cite this

    Meisel, M., Hermann-Kleiter, N., Hinterleitner, R., Gruber, T., Wachowicz, K., Pfeifhofer-Obermair, C., Fresser, F., Leitges, M., Soldani, C., Viola, A., Kaminski, S., & Baier, G. (2013). The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses. Immunity, 38(1), 41-52. https://doi.org/10.1016/j.immuni.2012.09.021