Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2022; 28(26): 3150-3163
Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3150
Activation of natural killer T cells contributes to Th1 bias in the murine liver after 14 d of ethinylestradiol exposure
Meng-Zhi Zou, Wei-Chao Kong, Heng Cai, Meng-Tao Xing, Zi-Xun Yu, Xin Chen, Lu-Yong Zhang, Xin-Zhi Wang
Meng-Zhi Zou, Wei-Chao Kong, Heng Cai, Zi-Xun Yu, Xin Chen, Lu-Yong Zhang, Xin-Zhi Wang, New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China
Meng-Tao Xing, Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China
Lu-Yong Zhang, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, China
Author contributions: Zou MZ and Kong WC contributed equally to the work; Zou MZ, Kong WC, Yu ZX, and Chen X performed the experiments, collected data, and analyzed the data; Xing MT, Zhang LY, and Wang XZ contributed to the guidance of experiments and the final manuscript; Wang XZ and Xing MT designed the study; Wang XZ, Xing MT, Zou MZ and Cai H wrote the manuscript; All the authors have reviewed and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 82073948 and 81703626; and National Innovation and Entrepreneurship Training Program for Undergraduate, No. 202210316040Z.
Institutional animal care and use committee statement: All animal experiments involved in this study were performed under the Ethical Committee of China Pharmaceutical University and the Laboratory Animal Management Committee of Jiangsu Province guidelines (Approval No.: 2021-10-003).
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: No additional data are available.
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: Xin-Zhi Wang, PhD, Associate Research Scientist, New Drug Screening Center, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu Province, China. wangxz@cpu.edu.cn
Received: October 26, 2021
Peer-review started: October 26, 2021
First decision: April 16, 2022
Revised: April 25, 2022
Accepted: May 22, 2022
Article in press: May 22, 2022
Published online: July 14, 2022
Processing time: 260 Days and 4.9 Hours
Core Tip

Core Tip: In this study, we observed the production of both Th1 and Th2 cytokines by natural killer T (NKT) cells in the liver after 14 d of exposure to ethinylestradiol-induced cholestasis. The liver immune microenvironment was also skewed toward a Th1 bias mainly contributed by NKT cells. Invariant NKT cell deficiency robustly alleviated cholestatic liver damage and downregulated the associated signaling pathways, highlighting the pathogenic role and therapeutic potential of hepatic NKT cells in cholestatic liver diseases.