Bidirectional Crosstalk Between Intestinal Epithelium and Immune Microenvironment in Inflammatory Bowel Disease: Mechanisms and Therapeutic Implications
Year: 2026
Type: article
Abstract: Jinghan Shen,* Simin Du,* Yuyue Zhang, HongKun Li, XingYan Liu, Jie Jing School and Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Jing, School and Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China, Email [email protected]: Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is characterized by chronic mucosal inflammation driven by dysregulated interactions between intestinal epithelial cells (IECs) and immune components. This review systematically explores the dynamic interplay between epithelial barrier integrity and immune-microenvironmental regulation in IBD pathogenesis. We highlight the dual roles of innate immunity (neutrophils, macrophages, dendritic cells, and innate lymphoid cells) and adaptive immunity (Th1, Th17, and Treg cells) in orchestrating inflammatory cascades and mucosal repair. It also describes the interaction between microbial metabolites and the intestinal microenvironment.Key mechanisms include neutrophil extracellular trap (NET)-mediated epithelial damage, macrophage polarization modulated by ROS/NOX4 signaling, and IL-22/STAT3-driven epithelial regeneration. Additionally, we dissect the Wnt/β-catenin and bile acid-TGR5 (Takeda G-protein-coupled receptor 5) pathways in intestinal stem cell renewal. Emerging therapeutic strategies targeting epithelial-immune axes, such as anti-IL-23/IL-17 biologics and MSC-derived exosomes, are critically evaluated. By integrating recent advances in single-cell omics and preclinical models, this review underscores the necessity of precision medicine approaches to restore immune-epithelial homeostasis. This paper also introduces the current application of organoids—a novel emerging technology—in experimental research.Future research should prioritize spatial-temporal mapping of cellular interactions and leverage organoids to advance translational validation of dual-target therapies to bridge mechanistic insights into clinical practice.Keywords: intestinal epithelial cells, inflammatory, innate immunity, adoptive immunity, pathogenesis
Institution: Zunyi Medical University
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7120424599
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