Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells | Zendy

Sascha Rutz | Zendy; Nobuhiko Kayagaki | Zendy; Qui Phung | Zendy; Céline Eidenschenk | Zendy; Rajkumar Noubade | Zendy; Xiaoting Wang | Zendy; Justin Lesch | Zendy; Rongze Lu | Zendy; Kim Newton | Zendy; Oscar W. Huang | Zendy; Andrea G. Cochran | Zendy; Mark Vasser | Zendy; Benjamin P. Fauber | Zendy; Jason DeVoss | Zendy; Joshua D. Webster | Zendy; Lauri Diehl | Zendy; Zora Modrušan | Zendy; Donald S. Kirkpatrick | Zendy; Jennie R. Lill | Zendy; Wenjun Ouyang | Zendy; Vishva M. Dixit | Zendy

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Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells

Author(s) -

Sascha Rutz,

Nobuhiko Kayagaki,

Qui Phung,

Céline Eidenschenk,

Rajkumar Noubade,

Xiaoting Wang,

Justin Lesch,

Rongze Lu,

Kim Newton,

Oscar W. Huang,

Andrea G. Cochran,

Mark Vasser,

Benjamin P. Fauber,

Jason DeVoss,

Joshua D. Webster,

Lauri Diehl,

Zora Modrušan,

Donald S. Kirkpatrick,

Jennie R. Lill,

Wenjun Ouyang,

Vishva M. Dixit

Publication year - 2014

Publication title -

nature

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 15.993

H-Index - 1226

eISSN - 1476-4687

pISSN - 0028-0836

DOI - 10.1038/nature13979

Subject(s) - ubiquitin ligase , interleukin 17 , rar related orphan receptor gamma , deubiquitinating enzyme , ubiquitin , microbiology and biotechnology , t cell , interleukin 21 , biology , chemistry , inflammation , immunology , immune system , foxp3 , gene , biochemistry

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.

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