| Autor: |
Hao-Xian Zhu, Shu-Han Yang, Cai-Yue Gao, Zhen-Hua Bian, Xiao-Min Chen, Rong-Rong Huang, Qian-Li Meng, Xin Li, Haosheng Jin, Koichi Tsuneyama, Ying Han, Liang Li, Zhi-Bin Zhao, Gershwin, M. Eric, Zhe-Xiong Lian |
| Zdroj: |
Nature Communications; 4/5/2024, Vol. 15 Issue 1, p1-13, 13p, 6 Graphs |
| Abstrakt: |
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 antiCD8α 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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