Nuclear pore complex-mediated modulation of TCR signaling is required for naïve CD4+ T cell homeostasis.
Nat Immunol
; 19(6): 594-605, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29736031
ABSTRACT
Nuclear pore complexes (NPCs) are channels connecting the nucleus with the cytoplasm. We report that loss of the tissue-specific NPC component Nup210 causes a severe deficit of naïve CD4+ T cells. Nup210-deficient CD4+ T lymphocytes develop normally but fail to survive in the periphery. The decreased survival results from both an impaired ability to transmit tonic T cell receptor (TCR) signals and increased levels of Fas, which sensitize Nup210-/- naïve CD4+ T cells to Fas-mediated cell death. Mechanistically, Nup210 regulates these processes by modulating the expression of Cav2 (encoding Caveolin-2) and Jun at the nuclear periphery. Whereas the TCR-dependent and CD4+ T cell-specific upregulation of Cav2 is critical for proximal TCR signaling, cJun expression is required for STAT3-dependent repression of Fas. Our results uncover an unexpected role for Nup210 as a cell-intrinsic regulator of TCR signaling and T cell homeostasis and expose NPCs as key players in the adaptive immune system.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Linfócitos T CD4-Positivos
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Transdução de Sinais
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Complexo de Proteínas Formadoras de Poros Nucleares
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Homeostase
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article