| Literature DB >> 25470037 |
Sascha Rutz1, Nobuhiko Kayagaki2, Qui T Phung3, Celine Eidenschenk1, Rajkumar Noubade1, Xiaoting Wang1, Justin Lesch1, Rongze Lu1, Kim Newton2, Oscar W Huang4, Andrea G Cochran4, Mark Vasser3, Benjamin P Fauber5, Jason DeVoss1, Joshua Webster6, Lauri Diehl6, Zora Modrusan7, Donald S Kirkpatrick3, Jennie R Lill3, Wenjun Ouyang1, Vishva M Dixit2.
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-β signalling. Our data identify DUBA as a cell-intrinsic suppressor of IL-17 production.Entities:
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Year: 2014 PMID： 25470037 DOI： 10.1038/nature13979
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962