Lusetti F, Bezzio C, De Bernardi A, Dota M, Manes G, Saibeni S
Gastroenterology Unit, Foundation Policlinico San Matteo IRCCS, University of Pavia, Pavia, Italy.
IBD Center, Gastroenterology Unit, Rho Hospital, ASST Rhodense, Rho, Italy.
Expert Rev Gastroenterol Hepatol. 2025 Jan;19(1):15-25. doi: 10.1080/17474124.2025.2450795. Epub 2025 Jan 8.
Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), present ongoing challenges despite advances in pathophysiological understanding and therapeutic options. Current therapies often fail to achieve sustained remission, necessitating exploration of novel treatment targets.
This review explores the role of Tumor Necrosis Factor-like cytokine 1A (TL1A) and its receptor DR3 in IBD pathogenesis, detailing their involvement in mucosal homeostasis and immune modulation. Recent studies on TL1A inhibitors highlight their potential in mitigating inflammation and fibrosis in IBD.
TL1A inhibition emerges as a promising therapeutic strategy, supported by encouraging outcomes in clinical trials for moderate to severe IBD. Future research may elucidate TL1A's broader impact on immunity, epithelial integrity and fibrosis, offering new avenues for therapeutic intervention and biomarker discovery. Ongoing phase 3 trials are pivotal in assessing TL1A inhibitors as effective and safe treatments for IBD. Additionally, exploration of TL1A's role in fibrosis-associated complications and its potential as a biomarker for treatment response holds promise for personalized medicine approaches. Consideration of TL1A inhibition in concurrent immune-mediated inflammatory diseases suggests broader therapeutic implications beyond gastrointestinal manifestations of IBD.
炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），尽管在病理生理学理解和治疗选择方面取得了进展，但仍面临持续挑战。目前的治疗方法往往无法实现持续缓解，因此有必要探索新的治疗靶点。
本综述探讨了肿瘤坏死因子样细胞因子1A（TL1A）及其受体DR3在IBD发病机制中的作用，详细阐述了它们在黏膜稳态和免疫调节中的作用。最近关于TL1A抑制剂的研究突出了其在减轻IBD炎症和纤维化方面的潜力。
TL1A抑制作为一种有前景的治疗策略出现，中度至重度IBD的临床试验结果令人鼓舞。未来的研究可能会阐明TL1A对免疫、上皮完整性和纤维化的更广泛影响，为治疗干预和生物标志物发现提供新途径。正在进行的3期试验对于评估TL1A抑制剂作为IBD有效且安全的治疗方法至关重要。此外，探索TL1A在纤维化相关并发症中的作用及其作为治疗反应生物标志物的潜力，有望实现个性化医疗方法。考虑在并发免疫介导的炎症性疾病中抑制TL1A，表明其治疗意义超出了IBD的胃肠道表现。
