Tettoni Enrico, Gabbiadini Roberto, Dal Buono Arianna, Privitera Giuseppe, Vadalà Vincenzo, Migliorisi Giulia, Bertoli Peter, Quadarella Alessandro, Bezzio Cristina, Armuzzi Alessandro
IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy.
Department of Gastroenterology and Endoscopy, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Brescia, Italy.
Int J Mol Sci. 2025 May 23;26(11):5017. doi: 10.3390/ijms26115017.
Inflammatory bowel diseases (IBD) are chronic disorders characterized by persistent inflammation of the gastrointestinal tract. Despite advances in treatment, a significant proportion of patients remain refractory to current therapies and develop complications, particularly fibrosis, leading to strictures and fistulae. Tumor necrosis factor-like ligand 1A (TL1A) has emerged as a promising new target for IBD treatment, due to its dual role in inflammatory and fibrotic pathways. TL1A, acting through its receptor death receptor 3 (DR3), orchestrates mucosal inflammation by enhancing T-cell activation and promoting pro-inflammatory mediator secretion. TL1A also drives intestinal fibrosis by activating fibroblasts and increasing collagen deposition. Clinical trials evaluating anti-TL1A monoclonal antibodies have shown encouraging efficacy and safety, with significant improvements in clinical remission rates, endoscopic healing, and histologic outcomes. Beyond IBD, TL1A overexpression has been implicated in other immune-mediated inflammatory diseases, highlighting its broader therapeutic potential. This review explores TL1A's role in IBD pathogenesis, the latest clinical trial data, and its involvement in extraintestinal inflammatory disorders, underscoring its potential as a novel precision-medicine target across multiple diseases.
炎症性肠病（IBD）是一种以胃肠道持续炎症为特征的慢性疾病。尽管治疗方法有所进步，但仍有相当一部分患者对当前治疗无效，并出现并发症，尤其是纤维化，导致肠狭窄和瘘管。肿瘤坏死因子样配体1A（TL1A）已成为IBD治疗一个有前景的新靶点，因为它在炎症和纤维化途径中具有双重作用。TL1A通过其受体死亡受体3（DR3）发挥作用，通过增强T细胞活化和促进促炎介质分泌来协调黏膜炎症。TL1A还通过激活成纤维细胞和增加胶原蛋白沉积来驱动肠道纤维化。评估抗TL1A单克隆抗体的临床试验显示出令人鼓舞的疗效和安全性，临床缓解率、内镜愈合和组织学结果都有显著改善。除了IBD，TL1A的过表达还与其他免疫介导的炎症性疾病有关，突出了其更广泛的治疗潜力。这篇综述探讨了TL1A在IBD发病机制中的作用、最新的临床试验数据及其在肠外炎症性疾病中的参与情况，强调了其作为多种疾病新型精准医学靶点的潜力。
