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

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Th17 Cells
Interleukin-17
Up-Regulation
Protein Kinase C
Transforming Growth Factors
Autoimmune Experimental Encephalomyelitis
Growth Factor Receptors
Interleukin-2
Cell Biology
protein kinase C kinase
Cytokines
DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Meisel, M., Hermann-Kleiter, N., Hinterleitner, R., Gruber, T., Wachowicz, K., Pfeifhofer-Obermair, C., ... 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

The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses. / Meisel, Marlies; Hermann-Kleiter, Natascha; Hinterleitner, Reinhard; Gruber, Thomas; Wachowicz, Katarzyna; Pfeifhofer-Obermair, Christa; Fresser, Friedrich; Leitges, Michael; Soldani, Cristiana; Viola, Antonella; Kaminski, Sandra; Baier, Gottfried.

In: Immunity, Vol. 38, No. 1, 24.01.2013, p. 41-52.

Research output: Contribution to journalArticle

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, vol. 38, no. 1, pp. 41-52. https://doi.org/10.1016/j.immuni.2012.09.021
Meisel M, Hermann-Kleiter N, Hinterleitner R, Gruber T, Wachowicz K, Pfeifhofer-Obermair C et al. The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses. Immunity. 2013 Jan 24;38(1):41-52. https://doi.org/10.1016/j.immuni.2012.09.021
Meisel, Marlies ; Hermann-Kleiter, Natascha ; Hinterleitner, Reinhard ; Gruber, Thomas ; Wachowicz, Katarzyna ; Pfeifhofer-Obermair, Christa ; Fresser, Friedrich ; Leitges, Michael ; Soldani, Cristiana ; Viola, Antonella ; Kaminski, Sandra ; Baier, Gottfried. / The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses. In: Immunity. 2013 ; Vol. 38, No. 1. pp. 41-52.
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