Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.
J Immunol
; 213(1): 40-51, 2024 07 01.
Article
em En
| MEDLINE
| ID: mdl-38809096
ABSTRACT
NK cells are innate immune effectors that kill virally infected or malignant cells. NK cell deficiency (NKD) occurs when NK cell development or function is impaired and variants in MCM4, GINS1, MCM10, and GINS4 result in NKD. Although NK cells are strongly impacted by mutational deficiencies in helicase proteins, the mechanisms underlying this specific susceptibility are poorly understood. In this study, we induced replication stress in activated NK cells or T cells by chemical and genetic methods. We found that the CD56bright subset of NK cells accumulates more DNA damage and replication stress during activation than do CD56dim NK cells or T cells. Aphidicolin treatment increases apoptosis of CD56bright NK cells through increased pan-caspase expression and decreases perforin expression in surviving cells. These findings show that sensitivity to replication stress affects NK cell survival and function and contributes to NKD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Ativação Linfocitária
/
Apoptose
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2024
Tipo de documento:
Article