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

Transforming growth-factor \u3b2 (TGF\u3b2) 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 TGF\u3b2 receptor (TGF\u3b2R) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGF\u3b2R pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C \u3b1 (PKC\u3b1) as a signaling intermediate specific to the Th17 cell subset in the activation of TGF\u3b2RI. We have shown that PKC\u3b1 physically interacts and functionally cooperates with TGF\u3b2RI to promote robust SMAD2-3 activation. Furthermore, PKC\u3b1-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