Review Article: TL1A Inhibitors in IBD ‐ Mechanistic Rationale and Clinical Evidence

BACKGROUND: Tumour necrosis factor-like ligand 1A (TL1A) and its receptor DR3 form a pivotal signalling dyad linking immune activation, epithelial barrier dysfunction and fibrogenesis in inflammatory bowel diseases. (IBD). AIMS: This narrative review summarizes the molecular biology of the TL1A-DR3 axis, its roles in intestinal inflammation, fibrosis, and extraintestinal manifestations, and the emerging therapeutic landscape of TL1A inhibition in IBD. METHODS: Narrative synthesis of preclinical, translational, and clinical literature on TL1A/DR3 in Crohn's disease and ulcerative colitis. RESULTS: TL1A overexpression drives Crohn's-like ileitis, barrier disruption, and fibrosis in models; blockade attenuates both inflammation and remodelling. TL1A inhibitors show clinical/endoscopic remission in early-phase moderate-severe IBD trials (e.g., tulisokibart, duvakitug), with phase 3 programs ongoing. CONCLUSION: TL1A-DR3 integrates mucosal immunity with stromal injury, positioning inhibitors as a novel class to overcome IBD therapeutic ceilings by targeting the inflammation-fibrosis continuum.