Qi WT, Jia XH, Xue KL, Wang JW, Liang L. Interleukin-33/suppression of tumorigenicity 2 signaling in gastric injury: From mechanistic validation to spatiotemporal precision. World J Gastroenterol 2026; 32(40): 119684 [DOI: 10.3748/wjg.119684]
Corresponding Author of This Article
Lei Liang, MD, PhD, Professor, Department of Ultrasound, Aerospace Center Hospital, No. 15 Yuquan Street, Haidian District, Beijing 100049, China. lianglei_csk@126.com
Research Domain of This Article
Biochemistry & Molecular Biology
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review-article
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Qi WT, Jia XH, Xue KL, Wang JW, Liang L. Interleukin-33/suppression of tumorigenicity 2 signaling in gastric injury: From mechanistic validation to spatiotemporal precision. World J Gastroenterol 2026; 32(40): 119684 [DOI: 10.3748/wjg.119684]
World J Gastroenterol. Oct 28, 2026; 32(40): 119684 Published online Oct 28, 2026. doi: 10.3748/wjg.119684
Interleukin-33/suppression of tumorigenicity 2 signaling in gastric injury: From mechanistic validation to spatiotemporal precision
Wan-Ting Qi, Xiao-Hua Jia, Kai-Lin Xue, Jing-Wen Wang, Lei Liang
Wan-Ting Qi, Xiao-Hua Jia, Jing-Wen Wang, Lei Liang, Department of Ultrasound, Aerospace Center Hospital, Beijing 100049, China
Wan-Ting Qi, College of Medical Imaging, Dalian Medical University, Dalian 116000, Liaoning Province, China
Kai-Lin Xue, Peking University Aerospace School of Clinical Medicine, Aerospace Center Hospital, Beijing 100049, China
Co-first authors: Wan-Ting Qi and Xiao-Hua Jia.
Author contributions: Jia XH wrote the original draft; Qi WT contributed to conceptualization, writing, reviewing and editing; Jia XH, Qi WT, Xue KL, Wang JW, and Liang L participated in drafting the manuscript; Qi WT and Jia XH have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper; and all authors have read and approved the final version of the manuscript.
AI contribution statement: The language polishing was carried out using the artificial intelligence tool ChatGPT (OpenAI), which aimed to improve English grammar, sentence structure and overall readability. This tool was not used to generate scientific content, nor was it involved in the research design, interpretation or conclusion formation. All the charts and images in the manuscript were created by the authors. No images generated by artificial intelligence were used.
Supported by the National Natural Science Foundation of China, No. 62371010.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Lei Liang, MD, PhD, Professor, Department of Ultrasound, Aerospace Center Hospital, No. 15 Yuquan Street, Haidian District, Beijing 100049, China. lianglei_csk@126.com
Received: February 12, 2026 Revised: April 14, 2026 Accepted: May 12, 2026 Published online: October 28, 2026 Processing time: 221 Days and 1.5 Hours
Abstract
The interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis is a key regulator of gastric mucosal injury, contributing to inflammatory amplification, epithelial cell death, and tissue remodeling. Recent studies, including those using ST2-deficient models, have reinforced its pathogenic role in acute gastric injury. However, the current literature still relies predominantly on static endpoint analyses, which are insufficient to explain the dynamic and context-dependent functions of IL-33/ST2 signaling across different stages of tissue damage and repair. In this opinion review, we propose shifting the focus from repeated pathway validation to identifying phase-specific regulatory switches and cell-specific functional transitions. We outline a spatiotemporal framework in which epithelial cells initiate injury through IL-33 release, macrophages and mast cells amplify inflammation in intermediate stages, and regulatory or stromal cells promote tissue repair at later stages. We further discuss how molecular imaging of IL-33, tumor necrosis factor-α, caspase-3, and related mediators may enable real-time in vivo tracking of pathway activity and disease progression. Finally, we address technical considerations in gastric imaging, including tissue penetration, spatial resolution, organ motion, and probe delivery. Integrating dynamic biology with molecular imaging may support spatiotemporal precision intervention in gastric injury.
Core Tip: Current studies have established the involvement of interleukin (IL)-33/suppression of tumorigenicity 2 signaling in gastric injury, but most evidence remains derived from static endpoint analyses. We propose that future progress depends on defining when, where, and in which cell populations this pathway shifts from injury-promoting to repair-associated functions. By integrating phase-specific biology with molecular imaging of IL-33, tumor necrosis factor alpha, cysteine-aspartic protease-3, and related targets, a spatiotemporal framework may be developed to identify therapeutic windows and support precision intervention in gastric mucosal injury.
