炎症性肠病（IBD）的病因很复杂，对于进一步了解和开发改进疗法还有很大空间。因此，建立可靠的 IBD 模型对于未来的发展至关重要。在这项研究中，人诱导多能干 (iPS) 细胞衍生的结肠类器官 (hiPSC-CO) 联合使用肿瘤坏死因子 α (TNF-α)、干扰素 γ (IFN-γ) 和白细胞介素 (IL) 进行治疗。 )-1β（3 种细胞因子 [3CK]），已知在 IBD 患者的血清中升高。在 3CK 处理的 hiPSC-CO 中观察到基质细胞的炎症反应和肠上皮细胞的损伤。将 3CK 处理的 hiPSC-CO 与溃疡性结肠炎 (UC) 患者结肠的分子特征进行比较，发现 3CK 处理的 hiPSC-CO 与 UC 患者的结肠相似。此外，在 3CK 处理的 hiPSC-CO 中观察到的炎症细胞因子产生的增加通过托法替尼治疗而减弱。我们的 UC 模型将成为了解其病理机制和确定有效治疗方法的重要工具。© 2024 作者。

The etiology of inflammatory bowel disease (IBD) is complex, with much room for a greater understanding and development of improved therapies. Therefore, establishing a reliable IBD model is crucial for future advancements. In this study, human induced pluripotent stem (iPS) cell-derived colon organoids (hiPSC-COs) were treated with a combination of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin (IL)-1β (3 cytokines [3CK]), known to be elevated in the serum of IBD patients. Inflammatory responses in stromal cells and damage to intestinal epithelial cells were observed in the 3CK-treated hiPSC-COs. Comparison of molecular signatures of 3CK-treated hiPSC-COs with those of ulcerative colitis (UC) patient's colon revealed that 3CK-treated hiPSC-COs resemble UC patient's colon. Furthermore, the elevated production of inflammatory cytokines observed in 3CK-treated hiPSC-COs was attenuated by treatment with tofacitinib. Our UC model will be an essential tool to understand its pathologic mechanisms and identify effective therapeutic approaches.© 2024 The Author(s).