論文 - 詳細
| RRC ID | 73014 |
|---|---|
| 著者 | Wang TW, Johmura Y, Suzuki N, Omori S, Migita T, Yamaguchi K, Hatakeyama S, Yamazaki S, Shimizu E, Imoto S, Furukawa Y, Yoshimura A, Nakanishi M. |
| タイトル | Blocking PD-L1-PD-1 improves senescence surveillance and ageing phenotypes. |
| ジャーナル | Nature |
| Abstract |
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. |
| 巻・号 | 611(7935) |
| ページ | 358-364 |
| 公開日 | 2022-11-1 |
| DOI | 10.1038/s41586-022-05388-4 |
| PII | 10.1038/s41586-022-05388-4 |
| PMID | 36323784 |
| MeSH | Aging* / immunology Aging* / metabolism Aging* / pathology Animals B7-H1 Antigen* / antagonists & inhibitors B7-H1 Antigen* / metabolism CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / pathology Inflammation / pathology Liver Mice Non-alcoholic Fatty Liver Disease Phenotype* Programmed Cell Death 1 Receptor* / antagonists & inhibitors Programmed Cell Death 1 Receptor* / metabolism Rejuvenation Single-Cell Analysis |
| IF | 42.779 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 370 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 12.5 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |