Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells.
Nature
; 518(7539): 417-21, 2015 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-25470037
ABSTRACT
T-helper type 17 (TH17) cells that produce the cytokines interleukin-17A (IL-17A) and IL-17F are implicated in the pathogenesis of several autoimmune diseases. The differentiation of TH17 cells is regulated by transcription factors such as RORγt, but post-translational mechanisms preventing the rampant production of pro-inflammatory IL-17A have received less attention. Here we show that the deubiquitylating enzyme DUBA is a negative regulator of IL-17A production in T cells. Mice with DUBA-deficient T cells developed exacerbated inflammation in the small intestine after challenge with anti-CD3 antibodies. DUBA interacted with the ubiquitin ligase UBR5, which suppressed DUBA abundance in naive T cells. DUBA accumulated in activated T cells and stabilized UBR5, which then ubiquitylated RORγt in response to TGF-ß signalling. Our data identify DUBA as a cell-intrinsic suppressor of IL-17 production.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
/
Interleucina-17
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Células Th17
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Proteases Específicas de Ubiquitina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nature
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos