| First Author | Meisel M | Year | 2013 |
| Journal | Immunity | Volume | 38 |
| Issue | 1 | Pages | 41-52 |
| PubMed ID | 23290522 | Mgi Jnum | J:193022 |
| Mgi Id | MGI:5467433 | Doi | 10.1016/j.immuni.2012.09.021 |
| Citation | Meisel M, et al. (2013) The Kinase PKCalpha Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses. Immunity 38(1):41-52 |
| abstractText | Transforming growth-factor beta (TGFbeta) 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 TGFbeta receptor (TGFbetaR) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGFbetaR pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C alpha (PKCalpha) as a signaling intermediate specific to the Th17 cell subset in the activation of TGFbetaRI. We have shown that PKCalpha physically interacts and functionally cooperates with TGFbetaRI to promote robust SMAD2-3 activation. Furthermore, PKCalpha-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. |
