論文 - 詳細
| RRC ID | 58233 |
|---|---|
| 著者 | Maeda N, Maruhashi T, Sugiura D, Shimizu K, Okazaki IM, Okazaki T. |
| タイトル | Glucocorticoids potentiate the inhibitory capacity of programmed cell death 1 by up-regulating its expression on T cells. |
| ジャーナル | J Biol Chem |
| Abstract |
The inhibitory co-receptor programmed cell death 1 (PD-1, Pdcd1) plays critical roles in the regulation of autoimmunity, anticancer immunity, and immunity against infections. Immunotherapies targeting PD-1 have revolutionized cancer management and instigated various trials of improved cancer immunotherapies. Moreover, extensive trials are underway to potentiate PD-1 function to suppress harmful immune responses. Here we found that both natural and synthetic glucocorticoids (GCs) up-regulate PD-1 on T cells without altering the expression levels of other co-receptors and cell surface molecules. GC-induced up-regulation of PD-1 depended on transactivation of PD-1 transcription mediated through the glucocorticoid receptor. We further found that a GC response element 2525 bp upstream of the transcription start site of Pdcd1 is responsible for GC-mediated transactivation. We also observed that in vivo administration of GCs significantly up-regulates PD-1 expression on tumor-infiltrating T cells. By analyzing T cells differing in PD-1 expression, we directly demonstrated that the amount of PD-1 on the cell surface correlates with its inhibitory effect. Accordingly, GCs potentiated the capacity of PD-1 to inhibit T cell activation, suggesting that this PD-1-mediated inhibition contributes, at least in part, to the anti-inflammatory and immunosuppressive effects of GCs. In light of the critical roles of PD-1 in the regulation of autoimmunity, we expect that the potentiation of PD-1 activity may offer a promising therapeutic strategy for managing inflammatory and autoimmune diseases. Our current findings provide a rationale for strategies seeking to enhance the inhibitory effect of PD-1 by increasing its expression level. |
| 巻・号 | 294(52) |
| ページ | 19896-19906 |
| 公開日 | 2019-12-27 |
| DOI | 10.1074/jbc.RA119.010379 |
| PII | S0021-9258(20)30013-2 |
| PMID | 31723031 |
| PMC | PMC6937557 |
| MeSH | Animals Anti-Inflammatory Agents / pharmacology CD8-Positive T-Lymphocytes / cytology CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / metabolism Cells, Cultured Dexamethasone / pharmacology Glucocorticoids / pharmacology* Mice Mice, Inbred BALB C Mice, Inbred C57BL Programmed Cell Death 1 Receptor / genetics Programmed Cell Death 1 Receptor / metabolism* Promoter Regions, Genetic Receptors, Glucocorticoid / metabolism T-Lymphocytes / cytology T-Lymphocytes / immunology T-Lymphocytes / metabolism Transcription Initiation Site Transcriptional Activation / drug effects Up-Regulation / drug effects* |
| IF | 4.238 |
| 引用数 | 2 |
| 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 | 7 |
| 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 | |
| 遺伝子材料 | B6N Mouse BAC clone (RDB07573) B6Ng01- 240G08 |