Deficiency in WDFY4 reduces the number of CD8+ T cells via reactive oxygen species-induced apoptosis.
Mol Immunol
; 139: 131-138, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34482201
ABSTRACT
WDFY4 (WD repeat and FYVE domain-containing 4) is a susceptibility gene involved in several autoimmune diseases and plays an important role in the immune system. However, it is not clear how WDFY4 affects T cells. We have generated a Wdfy4-knockout mouse and found that selective deficiency of Wdfy4 in T cells led to a reduction in the number of CD8+ T cells in the periphery, thus promoting tumor growth when mice were challenged with a transplantable tumor. Moreover, conditional ablation of Wdfy4 in T cells enhanced the apoptosis of CD8+ T cells and increased the intracellular levels of reactive oxygen species accompanied by the upregulation of Nox2. Mechanistically, the decrease in the CD8+ T-cell numbers in Wdfy4-knockout mice was associated with activation of the p53 pathway and inhibition of the extracellular signal-regulated kinase pathway. In addition, WDFY4 participated in cell proliferation. In conclusion, our results elucidate the biological role of WDFY4 in apoptosis and establish a link between WDFY4 and T cells.
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Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Apoptose
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Linfócitos T CD8-Positivos
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Peptídeos e Proteínas de Sinalização Intracelular
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article