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Cathepsin L Inhibition Prevents Murine Autoimmune Diabetes via Suppression of CD8+ T Cell Activity
https://tokushima-u.repo.nii.ac.jp/records/2000229
https://tokushima-u.repo.nii.ac.jp/records/20002298ba2d73d-8566-4ba9-96de-00313491e013
| 名前 / ファイル | ライセンス | アクション |
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pone_5_9_e12894.pdf (5 MB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||||
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| 公開日 | 2024-10-11 | |||||||||||||||||||
| アクセス権 | ||||||||||||||||||||
| アクセス権 | open access | |||||||||||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||||||||||
| 資源タイプ | ||||||||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||||||
| 出版社版DOI | ||||||||||||||||||||
| 関連識別子 | https://doi.org/10.1371/journal.pone.0012894 | |||||||||||||||||||
| 関連名称 | 10.1371/journal.pone.0012894 | |||||||||||||||||||
| 出版タイプ | ||||||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||||||
| タイトル | ||||||||||||||||||||
| タイトル | Cathepsin L Inhibition Prevents Murine Autoimmune Diabetes via Suppression of CD8+ T Cell Activity | |||||||||||||||||||
| タイトル別表記 | ||||||||||||||||||||
| その他のタイトル | Cathepsin L in Type 1 Diabetes | |||||||||||||||||||
| 著者 |
山田, 安希子
× 山田, 安希子× 石丸, 直澄
WEKO
1721
× 新垣, 理恵子× Katunuma, Nobuhiko
× 林, 良夫
WEKO
1659
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| 抄録 | ||||||||||||||||||||
| 内容記述 | Background: Type 1 diabetes (T1D) is an autoimmune disease resulting from defects in central and peripheral tolerance and characterized by T cell-mediated destruction of islet β cells. To determine whether specific lysosomal proteases might influence the outcome of a T cell–mediated autoimmune response, we examined the functional significance of cathepsin inhibition on autoimmune T1D-prone non-obese diabetic (NOD) mice. Methods and Findings: Here it was found that specific inhibition of cathepsin L affords strong protection from cyclophosphamide (CY)-induced insulitis and diabetes of NOD mice at the advanced stage of CD8+ T cell infiltration via inhibiting granzyme activity. It was discovered that cathepsin L inhibition prevents cytotoxic activity of CD8+ T cells in the pancreatic islets through controlling dipeptidyl peptidase I activity. Moreover, the gene targeting for cathepsin L with application of in vivo siRNA administration successfully prevented CY-induced diabetes of NOD mice. Finally, cathepsin L mRNA expression of peripheral CD8+ T cells from NOD mice developing spontaneous T1D was significantly increased compared with that from control mice. Conclusions: Our results identified a novel function of cathepsin L as an enzyme whose activity is essential for the progression of CD8+ T cell-mediated autoimmune diabetes, and inhibition of cathepsin L as a powerful therapeutic strategy for autoimmune diabetes. |
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| 書誌情報 |
en : PLOS ONE 巻 5, 号 9, p. e12894, 発行日 2010-09-22 |
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| 収録物識別子タイプ | EISSN | |||||||||||||||||||
| 収録物識別子 | 19326203 | |||||||||||||||||||
| 出版者 | ||||||||||||||||||||
| 出版者 | PLOS | |||||||||||||||||||
| 権利情報 | ||||||||||||||||||||
| 権利情報 | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||||||||||||||||
| EID | ||||||||||||||||||||
| 識別子 | 232552 | |||||||||||||||||||
| 言語 | ||||||||||||||||||||
| 言語 | eng | |||||||||||||||||||
