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Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X
The T cell hyperproliferation and autoimmune phenotypes that manifest in mice lacking E3 ubiquitin ligases such as Cbl, ITCH, or GRAIL highlight the importance of ubiquitination for the maintenance of peripheral T cell tolerance. Less is known, however, about the deubiquitinating enzymes that regula...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172213/ https://www.ncbi.nlm.nih.gov/pubmed/25200027 http://dx.doi.org/10.1084/jem.20140860 |
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author | Naik, Edwina Webster, Joshua D. DeVoss, Jason Liu, Jinfeng Suriben, Rowena Dixit, Vishva M. |
author_facet | Naik, Edwina Webster, Joshua D. DeVoss, Jason Liu, Jinfeng Suriben, Rowena Dixit, Vishva M. |
author_sort | Naik, Edwina |
collection | PubMed |
description | The T cell hyperproliferation and autoimmune phenotypes that manifest in mice lacking E3 ubiquitin ligases such as Cbl, ITCH, or GRAIL highlight the importance of ubiquitination for the maintenance of peripheral T cell tolerance. Less is known, however, about the deubiquitinating enzymes that regulate T cell proliferation and effector function. Here, we define a cell intrinsic role for the deubiquitinase Usp9X during proximal TCR signaling. Usp9X-deficient T cells were hypoproliferative, yet mice with T cell–specific Usp9x deletion had elevated numbers of antigen-experienced T cells and expanded PD-1 and OX40-expressing populations consistent with immune hyperactivity. Aged Usp9x KO mice developed lupus-like autoimmunity and lymphoproliferative disease, indicating that ubiquitin ligases and deubiquitinases maintain the delicate balance between effective immunity and self-tolerance. |
format | Online Article Text |
id | pubmed-4172213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41722132015-03-22 Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X Naik, Edwina Webster, Joshua D. DeVoss, Jason Liu, Jinfeng Suriben, Rowena Dixit, Vishva M. J Exp Med Brief Definitive Report The T cell hyperproliferation and autoimmune phenotypes that manifest in mice lacking E3 ubiquitin ligases such as Cbl, ITCH, or GRAIL highlight the importance of ubiquitination for the maintenance of peripheral T cell tolerance. Less is known, however, about the deubiquitinating enzymes that regulate T cell proliferation and effector function. Here, we define a cell intrinsic role for the deubiquitinase Usp9X during proximal TCR signaling. Usp9X-deficient T cells were hypoproliferative, yet mice with T cell–specific Usp9x deletion had elevated numbers of antigen-experienced T cells and expanded PD-1 and OX40-expressing populations consistent with immune hyperactivity. Aged Usp9x KO mice developed lupus-like autoimmunity and lymphoproliferative disease, indicating that ubiquitin ligases and deubiquitinases maintain the delicate balance between effective immunity and self-tolerance. The Rockefeller University Press 2014-09-22 /pmc/articles/PMC4172213/ /pubmed/25200027 http://dx.doi.org/10.1084/jem.20140860 Text en © 2014 Naik et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Naik, Edwina Webster, Joshua D. DeVoss, Jason Liu, Jinfeng Suriben, Rowena Dixit, Vishva M. Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X |
title | Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X |
title_full | Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X |
title_fullStr | Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X |
title_full_unstemmed | Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X |
title_short | Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X |
title_sort | regulation of proximal t cell receptor signaling and tolerance induction by deubiquitinase usp9x |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172213/ https://www.ncbi.nlm.nih.gov/pubmed/25200027 http://dx.doi.org/10.1084/jem.20140860 |
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