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

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

doi:10.1038/ni.3230

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

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

Medicine

Technion - Israel Institute of Technology

Research output: Contribution to journal › Article › peer-review

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 + γ δ 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.

Original language	English
Pages (from-to)	950-960
Number of pages	11
Journal	Nature Immunology
Volume	16
Issue number	9
DOIs	https://doi.org/10.1038/ni.3230
State	Published - 19 Aug 2015

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ni.3230

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Dufner, A., Kisser, A., Niendorf, S., Basters, A., Reissig, S., Schonle, A., Aichem, A., Kurz, T., Schlosser, A., Yablonski, D., Groettrup, M., Buch, T., Waisman, A., Schamel, W. W., Prinz, M., & Knobeloch, K. P. (2015). The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells. Nature Immunology, 16(9), 950-960. https://doi.org/10.1038/ni.3230

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

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 + γ δ 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.",

author = "Almut Dufner and Agnes Kisser and Sandra Niendorf and Anja Basters and Sonja Reissig and Anne Schonle and Annette Aichem and Thorsten Kurz and Andreas Schlosser and Deborah Yablonski and Marcus Groettrup and Thorsten Buch and Ari Waisman and Schamel, {Wolfgang W.} and Marco Prinz and Knobeloch, {Klaus Peter}",

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Dufner, A, Kisser, A, Niendorf, S, Basters, A, Reissig, S, Schonle, A, Aichem, A, Kurz, T, Schlosser, A, Yablonski, D, Groettrup, M, Buch, T, Waisman, A, Schamel, WW, Prinz, M & Knobeloch, KP 2015, 'The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells', Nature Immunology, vol. 16, no. 9, pp. 950-960. https://doi.org/10.1038/ni.3230

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AU - Dufner, Almut

AU - Kisser, Agnes

AU - Niendorf, Sandra

AU - Basters, Anja

AU - Reissig, Sonja

AU - Schonle, Anne

AU - Aichem, Annette

AU - Kurz, Thorsten

AU - Schlosser, Andreas

AU - Yablonski, Deborah

AU - Groettrup, Marcus

AU - Buch, Thorsten

AU - Waisman, Ari

AU - Schamel, Wolfgang W.

AU - Prinz, Marco

AU - Knobeloch, Klaus Peter

PY - 2015/8/19

Y1 - 2015/8/19

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AB - 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 + γ δ 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.

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JO - Nature Immunology

JF - Nature Immunology

IS - 9

ER -

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

Abstract

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