Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation.
Cell Rep
; 19(4): 746-759, 2017 04 25.
Article
em En
| MEDLINE
| ID: mdl-28445726
ABSTRACT
Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription. SIRT1 agonists reduce tumor growth in mice by blocking Th17 cell differentiation. In cancer patients, the SIRT1 agonist metformin reduced the frequency of Th17 cells and STAT3 acetylation levels. Altogether, these data underscore that SIRT1 activation impedes Th17 cell differentiation and thereby limits tumor growth and suggest that SIRT1 activators may directly target IL-17A functions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Transcrição STAT3
/
Sirtuína 1
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2017
Tipo de documento:
Article