The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells

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

The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells

Dateien

Dufner_0-298522.pdfGröße: 3.36 MBDownloads: 632

Datum

2015

Autor:innen

Dufner, Almut

Kisser, Agnes

Niendorf, Sandra

Basters, Anja

Reissig, Sonja

Schönle, Anne

Aichem, Annette

Kurz, Thorsten

Schlosser, Andreas

Yablonski, Deborah

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Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Nature Immunology. 2015, 16(9), pp. 950-960. ISSN 1529-2908. eISSN 1529-2916. Available under: doi: 10.1038/ni.3230

Zusammenfassung

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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

DUFNER, Almut, Agnes KISSER, Sandra NIENDORF, Anja BASTERS, Sonja REISSIG, Anne SCHÖNLE, Annette AICHEM, Thorsten KURZ, Andreas SCHLOSSER, Deborah YABLONSKI, Marcus GRÖTTRUP, Thorsten BUCH, Ari WAISMAN, Wolfgang W. SCHAMEL, Marco PRINZ, Klaus-Peter KNOBELOCH, 2015. The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells. In: Nature Immunology. 2015, 16(9), pp. 950-960. ISSN 1529-2908. eISSN 1529-2916. Available under: doi: 10.1038/ni.3230

BibTex

@article{Dufner2015-09ubiqu-31600,
  year={2015},
  doi={10.1038/ni.3230},
  title={The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells},
  number={9},
  volume={16},
  issn={1529-2908},
  journal={Nature Immunology},
  pages={950--960},
  author={Dufner, Almut and Kisser, Agnes and Niendorf, Sandra and Basters, Anja and Reissig, Sonja and Schönle, Anne and Aichem, Annette and Kurz, Thorsten and Schlosser, Andreas and Yablonski, Deborah and Gröttrup, Marcus and Buch, Thorsten and Waisman, Ari and Schamel, Wolfgang W. and Prinz, Marco and Knobeloch, Klaus-Peter}
}

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