The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells
Nature immunology. Bd. 16. H. 9. New York, NY: Nature America Inc. 2015 S. 950 - 960
Erscheinungsjahr: 2015
ISBN/ISSN: 1529-2916 ; 1529-2908
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
Doi/URN: 10.1038/ni.3230
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Inhaltszusammenfassung
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 14-3-3[beta]. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of...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 14-3-3[beta]. 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-7R[alpha] 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+ [gamma][delta] 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.» weiterlesen» einklappen
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Medizin
