The role of tight junctions in the pathogenesis of inflammatory bowel disease: immune modulation and barrier dysfunction

Abstract

Purpose of reviewThis review explores the molecular composition and regulatory mechanisms of intestinal tight junctions and their role in the pathophysiology of inflammatory bowel disease. We highlight the potential of tight junction-targeted therapeutic strategies as a promising approach to treat inflammatory bowel disease management.Recent findingsTight junctions are essential for regulating paracellular transport and maintaining intestinal homeostasis by forming a selective permeability barrier between epithelial cells. These multiprotein complexes compartmentalize the apical and basolateral membranes to modulate intercellular adhesion. However, the disruption of tight junctions allows harmful substances to penetrate the intestinal tissue, which impairs the mucosal immune system and triggers inflammatory responses. This disruption is closely associated with the pathogenesis of inflammatory bowel disease, in which tight junction dysfunction contributes to disease progression. In inflammatory bowel disease, an altered tight junction structure causes increased epithelial permeability, contributing to disease progression. Recent studies have shown that tight junction regulation is influenced by immune cell activation, the gut microbiome, and the release of proinflammatory cytokines, such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-1 beta. In addition, key signaling pathways, including Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase, and nuclear factor-kappa B, play an important role in tight junction disruption, leading to increased epithelial permeability. Thus, therapeutic strategies aimed at restoring tight junction integrity hold promise for the effective management and prevention of inflammatory bowel disease.