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

Autor: Rutz S; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Kayagaki N; Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Phung QT; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Eidenschenk C; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Noubade R; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Wang X; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Lesch J; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Lu R; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Newton K; Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Huang OW; Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Cochran AG; Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Vasser M; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Fauber BP; Discovery Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., DeVoss J; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Webster J; Department of Pathology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Diehl L; Department of Pathology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Modrusan Z; Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Kirkpatrick DS; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Lill JR; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Ouyang W; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA., Dixit VM; Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
Jazyk: angličtina
Zdroj: Nature [Nature] 2015 Feb 19; Vol. 518 (7539), pp. 417-21. Date of Electronic Publication: 2014 Dec 03.
DOI: 10.1038/nature13979
Abstrakt: 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.
Databáze: MEDLINE
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