論文 - 詳細
| RRC ID | 69680 |
|---|---|
| 著者 | Sugiura D, Okazaki IM, Maeda TK, Maruhashi T, Shimizu K, Arakaki R, Takemoto T, Ishimaru N, Okazaki T. |
| タイトル | PD-1 agonism by anti-CD80 inhibits T cell activation and alleviates autoimmunity. |
| ジャーナル | Nat Immunol |
| Abstract |
Targeted blockade of the checkpoint molecule programmed cell death 1 (PD-1) can activate tumor-specific T cells to destroy tumors, whereas targeted potentiation of PD-1 is expected to suppress autoreactive T cells and alleviate autoimmune diseases. However, the development of methods to potentiate PD-1 remains challenging. Here we succeeded in eliciting PD-1 function by targeting the cis-PD-L1-CD80 duplex, formed by binding of CD80 to the PD-1 ligand PD-L1, that attenuates PD-L1-PD-1 binding and abrogates PD-1 function. By generating anti-CD80 antibodies that detach CD80 from the cis-PD-L1-CD80 duplex and enable PD-L1 to engage PD-1 in the presence of CD80, we demonstrate that the targeted dissociation of cis-PD-L1-CD80 duplex elicits PD-1 function in the condition where PD-1 function is otherwise restricted. We demonstrate using murine models that the removal of PD-1 restriction is effective in alleviating autoimmune disease symptoms. Our findings establish a method to potentiate PD-1 function and propose the removal of restraining mechanisms as an efficient strategy to potentiate the function of inhibitory molecules. |
| 巻・号 | 23(3) |
| ページ | 399-410 |
| 公開日 | 2022-3-1 |
| DOI | 10.1038/s41590-021-01125-7 |
| PII | 10.1038/s41590-021-01125-7 |
| PMID | 35145298 |
| MeSH | Animals Autoimmune Diseases* Autoimmunity B7-1 Antigen B7-H1 Antigen / metabolism Mice Neoplasms* Programmed Cell Death 1 Receptor / metabolism T-Lymphocytes |
| IF | 20.479 |
| 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 | 37 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAJI(RCB1647) |