Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X.
J Exp Med
; 211(10): 1947-55, 2014 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-25200027
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endopeptidases
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Receptores de Antígenos de Linfócitos T
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Transdução de Sinais
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Autoimunidade
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Tolerância a Antígenos Próprios
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Transtornos Linfoproliferativos
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2014
Tipo de documento:
Article