Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Naik, Edwina, Webster, Joshua D., DeVoss, Jason, Liu, Jinfeng, Suriben, Rowena, Dixit, Vishva M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
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
_version_ 1782336017494179840
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
work_keys_str_mv AT naikedwina regulationofproximaltcellreceptorsignalingandtoleranceinductionbydeubiquitinaseusp9x
AT websterjoshuad regulationofproximaltcellreceptorsignalingandtoleranceinductionbydeubiquitinaseusp9x
AT devossjason regulationofproximaltcellreceptorsignalingandtoleranceinductionbydeubiquitinaseusp9x
AT liujinfeng regulationofproximaltcellreceptorsignalingandtoleranceinductionbydeubiquitinaseusp9x
AT suribenrowena regulationofproximaltcellreceptorsignalingandtoleranceinductionbydeubiquitinaseusp9x
AT dixitvishvam regulationofproximaltcellreceptorsignalingandtoleranceinductionbydeubiquitinaseusp9x