Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2023; 15(8): 787-806
Published online Aug 26, 2023. doi: 10.4252/wjsc.v15.i8.787
Interferon-gamma and tumor necrosis factor-alpha synergistically enhance the immunosuppressive capacity of human umbilical-cord-derived mesenchymal stem cells by increasing PD-L1 expression
Zhuo Chen, Meng-Wei Yao, Zhi-Lin Shen, Shi-Dan Li, Wei Xing, Wei Guo, Zhan Li, Xiao-Feng Wu, Luo-Quan Ao, Wen-Yong Lu, Qi-Zhou Lian, Xiang Xu, Xiang Ao
Zhuo Chen, Meng-Wei Yao, Zhi-Lin Shen, Wei Xing, Wei Guo, Zhan Li, Xiao-Feng Wu, Luo-Quan Ao, Xiang Xu, Xiang Ao, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China
Zhuo Chen, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China
Shi-Dan Li, Department of Orthopedics, Daping Hospital, Army Medical University, Chongqing 400042, China
Wen-Yong Lu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, The South of Shangcai Village, Wenzhou 325005, Zhejiang Province, China
Qi-Zhou Lian, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
Xiang Ao, Department of Orthopedics, 953 Hospital of PLA Army, Shigatse Branch of Xinqiao Hospital, Army Medical University, Shigatse 857000, Tibet Autonomous Region, China
Author contributions: Chen Z and Yao MW contributed equally to this work; Chen Z and Yao MW designed all the project and the experiment; Chen Z, Ao X, Guo W, Xing W, Shen ZL, and Lian QZ developed the methodology; Chen Z, Yao MW, and Ao LQ performed the in vivo experiments; Chen Z, Yao MW, Li Z, Li SD, and Lu WY performed the in vitro experiments; Chen Z and Ao X wrote the manuscript; Xu X, Ao X, and Chen Z reviewed and edited the paper; and all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81871568 and No. 32100643; and COVID-19 Infection and Prevention Emergency Special Project of Chongqing Education Commission, No. KYYJ202009.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Army Medical University (SYXK2022-0018).
Conflict-of-interest statement: The authors confirm that this article has no conflict of interest to report.
Data sharing statement: Data sets used or analyzed during the current study can be obtained reasonably request of the corresponding authors.
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: Xiang Ao, PhD, Researcher, Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Changjiang Road, Yuzhong District, Chongqing 40042, China. ax_syd@163.com
Received: March 13, 2023
Peer-review started: March 13, 2023
First decision: June 6, 2023
Revised: June 20, 2023
Accepted: July 24, 2023
Article in press: July 24, 2023
Published online: August 26, 2023
Processing time: 165 Days and 4.6 Hours
Core Tip

Core Tip: Our study showed that interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) significantly induced programmed cell death protein 1 ligand 1 (PD-L1) expression in human umbilical-cord-mesenchymal stem cells (hUC-MSCs), and pretreated hUC-MSCs exhibited stronger immunomodulatory capacity. Signaling pathway analysis showed that TNF-α up-regulated IFN-γ receptor expression in hUC-MSCs through nuclear factor kappa-B pathway, and then promoted IFN-γ -mediated activation of JAK/STAT1/interferon regulatory factor 1 pathway and PD-L1 expression. In ulcerative colitis mice, hUC-MSCs pretreated with IFN-γ and TNF-α exhibited stronger immunosuppressive ability through high expression of PD-L1, effectively inhibited the inflammation in the colon of mice.