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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Liver infiltration of multiple immune cells during the process of acute liver injury and repair
Yuan Xie, Ke-Bo Zhong, Yang Hu, Yong-Lun Xi, Shi-Xing Guan, Meng Xu, Yuan Lin, Feng-Yong Liu, Wei-Jie Zhou, Yi Gao
Yuan Xie, Ke-Bo Zhong, Yi Gao, General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
Yang Hu, Yong-Lun Xi, Shi-Xing Guan, Wei-Jie Zhou, State Key Laboratory of Organ Failure Research, Department of Pathology, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Meng Xu, Yuan Lin, Wei-Jie Zhou, Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, First Clinical Medical School, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Feng-Yong Liu, Department of Interventional Radiology, Senior Department of Oncology, Fifth Medical Center of PLA General Hospital, Beijing 100853, China
Yi Gao, State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510280, Guangdong Province, China
Author contributions: Xie Y designed the experiments and wrote the manuscript; Zhong KB and Hu Y performed statistic and bioinformatic analyses; Xie Y, Zhong KB and Hu Y contributed equally to this work; Xi YL, Guan SX, Xu M, Lin Y helped to perform the experiments; Gao Y and Zhou WJ conceived the project; Liu FY supervised the schedule progress of the project; Gao Y, Zhou WJ and Liu FY were co-corresponding authors, and they contributed equally to this project; all authors have read and approved the final manuscript.
Supported by the National Key R&D Program of China, No. 2018YFA0108200 and No. 2018YFC1106400; the National Natural Science Foundation of China, No. 31972926, No. 32000607, No. 82270645 and No. 92068206; Guangdong Basic and Applied Basic Research Foundation, No. 2020A1515111111 and No. 2019A1515110145; and China Postdoctoral Science Foundation, No. 2019M660205.
Institutional animal care and use committee statement: Animal-related research protocols were consistent with the US Public Health Service Policy on Use of Laboratory Animals, and were approved by the Ethics Committee on Use and Care of Animals of Southern Medical University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data and materials of this study are available from Zhou WJ (weijiezhouum@163.com) upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Yi Gao, MD, Doctor, General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, No. 253 Gongye Middle Avenue, Haizhu District, Guangzhou 510280, Guangdong Province, China. gaoyi6146@163.com
Received: September 30, 2022
Peer-review started: September 30, 2022
First decision: October 21, 2022
Revised: October 29, 2022
Accepted: November 18, 2022
Article in press: November 18, 2022
Published online: December 14, 2022
ARTICLE HIGHLIGHTS
Research background
Immune cells, including neutrophils, natural killer (NK) cells, T cells, NKT cells and macrophages, participate in the progression of acute liver injury and hepatic recovery. leukocyte cell-derived chemotaxin 2 (LECT2) is a pleiotropic protein that not only functions as a cytokine to exhibit chemotactic properties but also plays multifunctional roles in some physiological conditions and pathological abnormalities.
Research motivation
To date, there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery. LECT2 regulates chronic liver fibrogenesis, but its role in acute liver injury is unclear.
Research objectives
To investigate the infiltration changes of various immune cells in acute liver injury mouse models over time and to study the relationship between the changes in LECT2 and the infiltration of several immune cells.
Research methods
Carbon tetrachloride (CCl4)- and concanavalin A (ConA)-induced acute liver injury mouse models were employed to mimic toxin-induced and autoimmune-mediated liver injury, respectively. Immunohistochemical staining was used to indicate immune cells, and the quantitative changes in various immune cells were monitored at different time points. The levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBil) were measured by an automated chemical analyzer. The expression of LECT2 in liver tissues was detected by quantitative real-time polymerase chain reaction and the levels of LECT2 in serum were tested by enzyme-linked immunosorbent assay. Transwell assays were used to assess the chemotactic effect of LECT2 on THP-1 monocytes.
Research results
During the injury and repair process, different types of immune cells began to increase, reached their peaks and fell into decline at different time points. Furthermore, when the serum ALT and AST indices reverted to normal levels 7 d after injury, the infiltration of immune cells still existed even 14 d after injury, showing an obvious lag effect. The expression of LECT2 was up-regulated in acute liver injury models, and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice. Compared with wild-type mice, Lect2-KO mice had different immune cell infiltration.
Research conclusions
The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair. LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.
Research perspectives
Our study indicated the potential roles of these immune cells and proposed a therapeutic concept that acute liver injury might be treated by regulating different immune cells at different time points.
