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World J Gastroenterol. Jun 14, 2026; 32(22): 117194
Published online Jun 14, 2026. doi: 10.3748/wjg.v32.i22.117194
Published online Jun 14, 2026. doi: 10.3748/wjg.v32.i22.117194
Mechanism of anti-HuD autoantibody inducing enteric neuronal apoptosis of irritable bowel syndrome and its potential for targeted intervention
Yu Zhang, Chen Zhu, Su-Hong Xia, Ming-Yu Zhang, Yi-Ran Liu, Jia-Lun Guan, Yu-Jie Huang, Kai Zhao, Jia-Zhi Liao, Wen-Juan Fan, Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Yu Zhang, Chen Zhu, Su-Hong Xia, Ming-Yu Zhang, Yi-Ran Liu, Jia-Lun Guan, Yu-Jie Huang, Kai Zhao, Jia-Zhi Liao, Wen-Juan Fan, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Jia-Zhi Liao, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Co-corresponding authors: Jia-Zhi Liao and Wen-Juan Fan.
Author contributions: Fan WJ, Xia SH, Zhang Y, and Liao JZ conceived and designed the study; Zhang Y and Fan WJ analyzed the data; Zhang Y, Fan WJ, Zhu C, Liu YR, Guan JL, Huang YJ, Zhao K, and Zhang MY contributed to conducting of the experiments and acquiring the data; Zhang Y, Zhu C, Liu YR, Guan JL, Huang YJ, Zhao K, and Zhang MY provided reagents; Fan WJ and Zhang Y drafted the manuscript; Fan WJ provided critical guidance on the in vivo experiment and secured key funding; Liao JZ supervised the in vitro experiment and ensured proper and comprehensive data quality control; Liao JZ and Fan WJ were jointly responsible for study oversight, critical revision of the manuscript for intellectual content, and addressing reviewers’ comments; their shared leadership and accountability justify co-corresponding authorship. All authors read and approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 82100568; and Key Research and Development Program of Hubei Province of China, No. 2023BCB003.
Institutional animal care and use committee statement: All animal experimental procedures were reviewed and approved by the Animal Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. TJH-202204019.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Wen-Juan Fan, PhD, Associate Chief Physician, Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan 430030, Hubei Province, China. juanwenfan1989@tjh.tjmu.edu.cn
Received: December 3, 2025
Revised: January 30, 2026
Accepted: March 17, 2026
Published online: June 14, 2026
Processing time: 179 Days and 6.3 Hours
Revised: January 30, 2026
Accepted: March 17, 2026
Published online: June 14, 2026
Processing time: 179 Days and 6.3 Hours
Core Tip
Core Tip: Current evidence indicates that immune dysregulation contributes to the pathogenesis of irritable bowel syndrome (IBS). However, the direct effects of autoantibodies on the enteric nervous system are unclear. This study established an antibody-mediated IBS model and demonstrated that anti-HuD autoantibodies directly induced enteric neuronal apoptosis by disrupting HuD-mediated RNA regulation. HuD autoantibodies reduced the stability of downstream mRNA and suppressed phosphatidylinositol 3-kinase-protein kinase B signaling, leading to neuronal loss and IBS-like gastrointestinal dysfunction. Pharmacological activation of protein kinase C restored HuD expression and alleviated neuronal apoptosis, highlighting a potential targeted therapeutic strategy for IBS associated with autoimmune-mediated enteric neuropathy.