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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Gene Expression Regulation
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein / adverse effects
  • Peptide Fragments / adverse effects
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism*
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction
  • Smad Proteins / metabolism
  • Substrate Specificity
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism*


  • Interleukin-17
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • myelin oligodendrocyte glycoprotein (35-55)
  • Protein Kinase C-alpha