The kinase PKCα selectively upregulates interleukin-17A during Th17 cell immune responses.
Immunity
; 38(1): 41-52, 2013 Jan 24.
Article
em En
| MEDLINE
| ID: mdl-23290522
ABSTRACT
Transforming growth-factor ß (TGFß) 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 TGFß receptor (TGFßR) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGFßR 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 TGFßRI. We have shown that PKCα physically interacts and functionally cooperates with TGFßRI 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-17
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Proteína Quinase C-alfa
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Células Th17
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Áustria