Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells
| Autor: | Kim Newton, Jennie R. Lill, Mark Vasser, Zora Modrusan, Jason DeVoss, Rajkumar Noubade, Oscar W. Huang, Donald S. Kirkpatrick, Vishva M. Dixit, Qui T. Phung, Joshua D. Webster, Andrea G. Cochran, Benjamin Fauber, Justin Lesch, Rongze Lu, Lauri Diehl, Xiaoting Wang, Sascha Rutz, Nobuhiko Kayagaki, Celine Eidenschenk, Wenjun Ouyang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Proteasome Endopeptidase Complex
Ubiquitin-Protein Ligases Inflammation Lymphocyte Activation Substrate Specificity Mice Ubiquitin Transforming Growth Factor beta RAR-related orphan receptor gamma Enzyme Stability Intestine Small medicine Animals Transcription factor Multidisciplinary biology Interleukin-17 Ubiquitination Transforming growth factor beta Nuclear Receptor Subfamily 1 Group F Member 3 Acquired immune system Research Highlight Ubiquitin ligase Cell biology Mice Inbred C57BL Protein Biosynthesis Immunology biology.protein Th17 Cells Female Ubiquitin-Specific Proteases Interleukin 17 medicine.symptom Protein Binding Signal Transduction |
| Zdroj: | Nature. 518:417-421 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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: | OpenAIRE |
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