Upregulation of PD-L1 in Senescence and Aging.
Mol Cell Biol
; 42(10): e0017122, 2022 10 20.
Article
em En
| MEDLINE
| ID: mdl-36154662
ABSTRACT
Cellular senescence is a stable form of cell cycle arrest associated with proinflammatory responses. Senescent cells can be cleared by the immune system as a part of normal tissue homeostasis. However, senescent cells can also accumulate in aged and diseased tissues, contributing to inflammation and disease progression. The mechanisms mediating the impaired immune-mediated clearance of senescent cells are poorly understood. Here, we report that senescent cells upregulate the immune checkpoint molecule PD-L1, the ligand for PD-1 on immune cells, which drives immune cell inactivation. The induction of PD-L1 in senescence is dependent on the proinflammatory program. Furthermore, the secreted factors released by senescent cells are sufficient to upregulate PD-L1 in nonsenescent control cells, mediated by the JAK-STAT pathway. In addition, we show that prolongevity intervention rapamycin downregulates PD-L1 in senescent cells. Last, we found that PD-L1 is upregulated in several tissues in naturally aged mice and in the lungs of idiopathic pulmonary fibrosis patients. Together, our results report that senescence and aging are associated with upregulation of a major immune checkpoint molecule, PD-L1. Targeting PD-L1 may offer new therapeutic opportunities in treating senescence and age-associated diseases.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Janus Quinases
/
Antígeno B7-H1
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos