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LAG-3 Knockout Exacerbates Immune Liver Injury |
WAN Yue1,ZHOU Bin2,GAO Rui2,CHEN Hui2,GAO Miao-miao2,WANG Xiao-fang3,DONG Dian-dian3,XIANG Shen-si2,YANG Xiao-ming1,2,**(),YU Miao1,2,3,**() |
1 School of Basic Medicine, Anhui Medical University, Hefei 230032, China 2 Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China 3 School of Life Sciences, Hebei University, Baoding 071002, China |
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Abstract Objective: To investigate the function and mechanism of lymphocyte activation gene 3 (LAG-3) in immune induced liver injury. Methods: Acute immune liver injury model in mice was induced by tail vein injection of concanavalin A (Con A). LAG-3 expression in hepatic immune cells was determined by flow cytometry and real-time PCR. LAG-3 knockout mice were utilized to study the effect of LAG-3 on Con A-induced immune liver injury. Peripheral blood was collected at different time points after Con A injection, and the serum levels of ALT, AST, and cytokines were detected. Liver tissue samples were collected for hematoxylin eosin staining (H & E, hematoxylin eosin staining) and the necrotic area of liver tissue was counted. Intrahepatic immune cell subsets and T cell activation were determined by flow cytometry. The expression of inflammation related genes was detected by real-time quantitative PCR. Yeast two-hybrid screening was performed to find LAG-3 interacting proteins. Results: Con A induced an increase in LAG-3 expression on hepatic immune cells; LAG-3 knockout exacerbated Con A-induced elevation of serum transaminase levels, increased necrotic area of the liver, and delayed resolution of inflammation in mice; LAG-3 knockout did not affect Con A-induced intrahepatic immune cell infiltration; LAG-3 knockout suppressed regulatory T cell expansion and IL-10 expression; MHCII accessory molecule CD74 interacted with LAG-3. Conclusions: LAG-3 knockout aggravates immune liver injury.
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Received: 10 April 2023
Published: 05 September 2023
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Cite this article:
WAN Yue, ZHOU Bin, GAO Rui, CHEN Hui, GAO Miao-miao, WANG Xiao-fang, DONG Dian-dian, XIANG Shen-si, YANG Xiao-ming, YU Miao. LAG-3 Knockout Exacerbates Immune Liver Injury. China Biotechnology, 2023, 43(8): 38-51.
URL:
https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2304017 OR https://manu60.magtech.com.cn/biotech/Y2023/V43/I8/38
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