Schlegel Nicolas
J Clin Invest. 2025 May 15;135(10). doi: 10.1172/JCI192640.
Inflammatory Bowel Diseases (IBD), including Crohn's disease and ulcerative colitis, pose challenges due to their complex pathophysiology and high prevalence. Despite advances in immune-targeted therapies, a substantial number of patients fail to achieve mucosal healing, highlighting the need for alternative therapeutic strategies. In this issue of the JCI, D'Addio et al. identified another mechanism underlying impaired epithelial regeneration in Crohn's disease. They found that abnormal cell death in intestinal epithelial stem cells, mediated by altered TMEM219 signaling, led to impaired mucosal healing. Targeting TMEM219 with ecto-TMEM219, which blocks its activation, restored stem cell function and promoted mucosal healing in vitro and in vivo. These findings suggest a promising therapeutic avenue focusing on epithelial repair. Additionally, patient-derived organoids (PDOs) emerge as a valuable tool for personalized treatment strategies and for advancing the field of IBD research. This study underscores the importance of epithelial cell biology in developing innovative IBD therapies.
炎症性肠病（IBD），包括克罗恩病和溃疡性结肠炎，因其复杂的病理生理学和高患病率而带来挑战。尽管免疫靶向治疗取得了进展，但仍有相当数量的患者未能实现黏膜愈合，这凸显了替代治疗策略的必要性。在本期《临床研究杂志》（JCI）中，达迪奥等人确定了克罗恩病上皮再生受损的另一种机制。他们发现，由改变的跨膜蛋白219（TMEM219）信号介导的肠道上皮干细胞异常细胞死亡导致黏膜愈合受损。用胞外TMEM219靶向TMEM219，阻断其激活，可恢复干细胞功能，并在体外和体内促进黏膜愈合。这些发现提示了一条专注于上皮修复的有前景的治疗途径。此外，患者来源的类器官（PDO）成为个性化治疗策略和推进IBD研究领域的有价值工具。这项研究强调了上皮细胞生物学在开发创新IBD疗法中的重要性。
