老化
衰老
免疫系统
炎症
CD8型
表型
程序性细胞死亡
免疫检查点
体内
细胞生物学
生物
人口
癌症研究
免疫学
免疫疗法
细胞凋亡
医学
生物化学
遗传学
环境卫生
基因
作者
Teh-Wei Wang,Yoshikazu Johmura,Shosaku Narumi,Satotaka Omori,Toshiro Migita,Kiyoshi Yamaguchi,Seira Hatakeyama,Satoshi Yamazaki,Eigo Shimizu,Seiya Imoto,Yoichi Furukawa,Akihiko Yoshimura,Makoto Nakanishi
出处
期刊:Nature
[Springer Nature]
日期:2022-11-02
卷期号:611 (7935): 358-364
被引量:101
标识
DOI:10.1038/s41586-022-05388-4
摘要
The accumulation of senescent cells is a major cause of age-related inflammation and predisposes to a variety of age-related diseases1. However, little is known about the molecular basis underlying this accumulation and its potential as a target to ameliorate the ageing process. Here we show that senescent cells heterogeneously express the immune checkpoint protein programmed death-ligand 1 (PD-L1) and that PD-L1+ senescent cells accumulate with age in vivo. PD-L1− cells are sensitive to T cell surveillance, whereas PD-L1+ cells are resistant, even in the presence of senescence-associated secretory phenotypes (SASP). Single-cell analysis of p16+ cells in vivo revealed that PD-L1 expression correlated with higher levels of SASP. Consistent with this, administration of programmed cell death protein 1 (PD-1) antibody to naturally ageing mice or a mouse model with normal livers or induced nonalcoholic steatohepatitis reduces the total number of p16+ cells in vivo as well as the PD-L1+ population in an activated CD8+ T cell-dependent manner, ameliorating various ageing-related phenotypes. These results suggest that the heterogeneous expression of PD-L1 has an important role in the accumulation of senescent cells and inflammation associated with ageing, and the elimination of PD-L1+ senescent cells by immune checkpoint blockade may be a promising strategy for anti-ageing therapy.
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