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- Title
The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells.
- Authors
Dufner, Almut; Kisser, Agnes; Niendorf, Sandra; Basters, Anja; Reissig, Sonja; Schönle, Anne; Aichem, Annette; Kurz, Thorsten; Schlosser, Andreas; Yablonski, Deborah; Groettrup, Marcus; Buch, Thorsten; Waisman, Ari; Schamel, Wolfgang W; Prinz, Marco; Knobeloch, Klaus-Peter
- Abstract
The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Rα mediated by the transcription factor Foxo1. Mice with T cell-specific USP8 deficiency developed colitis that was promoted by disturbed T cell homeostasis, a predominance of CD8+ γδ T cells in the intestine and impaired regulatory T cell function. Collectively, our data reveal an unexpected role for USP8 as an immunomodulatory DUB in T cells.
- Subjects
UBIQUITIN; PROTEOLYTIC enzymes; HOMEOSTASIS; T cells; CD8 antigen; IMMUNOREGULATION
- Publication
Nature Immunology, 2015, Vol 16, Issue 9, p950
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.3230