Glucocorticoids potentiate the inhibitory capacity of programmed cell death 1 by up-regulating its expression on T cells 52

• Material Type: 博士論文
• ISSN: 1083-351X
• Title: Glucocorticoids potentiate the inhibitory capacity of programmed cell death 1 by up-regulating its expression on T cells
• Volume: 294 52
• Author/Editor: Maeda, Natsumi; Maruhashi, Takumi; Sugiura, Daisuke; Shimizu, Kenji; Okazaki, Il-mi; Okazaki, Taku
• Author Heading: Maeda, Natsumi; Maruhashi, Takumi; Sugiura, Daisuke; Shimizu, Kenji; Okazaki, Il-mi; Okazaki, Taku
• Publication, Distribution, etc.: American Society for Biochemistry and Molecular Biology
• Publication Date: 2019-11-13
• Publication Date (W3CDTF): 2019-11-13
• Alternative Title: グルココルチコイドはT細胞上のPD-1の発現量を増加することによりPD-1による抑制効果を高める; Glucocorticoids strengthen PD-1 effects
• Periodical title: Journal of Biological Chemistry
• Degree grantor/type: 徳島大学
• Date Granted: 2020-03-23
• Date Granted (W3CDTF): 2020-03-23
• Dissertation Number: 甲第3358号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3358号
• Text Language Code: eng
• Subject Heading: immunology; immunosuppression; T cell; T cell receptor; gene expression; glucocorticoid; cytokine induction; PD-1; co-receptor; immune-checkpoint
• Target Audience: 一般
• Note (General): The inhibitory co-receptor programmed cell death 1 (PD-1, Pdcd1) plays critical roles in the regulation of autoimmunity, anti-cancer 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 in order 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. The GC-induced up-regulation of PD-1 depended on the transactivation of PD-1 transcription mediated through the glucocorticoid receptor (GR). We further found that a GC response element (GRE) 2525 bp upstream from 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 regulation, 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.
• DOI: info:doi/10.1074/jbc.RA119.010379; https://doi.org/info:doi/10.1074/jbc.RA119.010379
• Persistent ID (NDL): info:ndljp/pid/11498508; https://dl.ndl.go.jp/pid/11498508
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-06-07T00:39:19+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/114679
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp