| Item type |
文献 / Documents(1) |
| 公開日 |
2024-10-24 |
| 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 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1038/s41467-024-46654-5 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1038/s41467-024-46654-5 |
| 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 |
Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis |
|
言語 |
en |
| 著者 |
Zhu, Hao-Xian
Yang, Shu-Han
Gao, Cai-Yue
Bian, Zhen-Hua
Chen, Xiao-Min
Huang, Rong-Rong
Meng, Qian-Li
Li, Xin
Jin, Haosheng
常山, 幸一
Han, Ying
Li, Liang
Zhao, Zhi-Bin
Gershwin, M.Eric
Lian, Zhe-Xiong
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells. |
|
言語 |
en |
| 書誌情報 |
en : Nature Communications
巻 15,
p. 2936,
発行日 2024-04-05
|
| 収録物ID |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
20411723 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12645905 |
| 出版者 |
|
|
出版者 |
Springer Nature |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| EID |
|
|
識別子 |
406338 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
ncomms_15_2936.pdf (5.1 MB)
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