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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

Autoren


Dufner, Almut (Autor)
Kisser, Agnes (Autor)
Niendorf, Sandra (Autor)
Basters, Anja (Autor)
Reissig, Sonja (Autor)
Schönle, Anne (Autor)
Aichem, Annette (Autor)
Kurz, Thorsten (Autor)
Schlosser, Andreas (Autor)
Yablonski, Deborah (Autor)
Groettrup, Marcus (Autor)
Buch, Thorsten (Autor)
Waisman, Ari (Autor)
Schamel, Wolfgang W. (Autor)
Prinz, Marco (Autor)
Knobeloch, Klaus-Peter (Autor)

Klassifikation


DDC Sachgruppe:
Medizin