核磷蛋白 1 (NPM1) 在骨髓增生异常综合征 (MDS) 和急性髓系白血病中常见突变。炎症性肠病（IBD）和MDS同时发生很常见，表明IBD和MDS之间存在密切关系。在这里，我们检查了 NPM1 在 IBD 和结肠炎相关结直肠癌 (CAC) 中的功能。 IBD 患者中 NPM1 表达降低。 Npm1 /- 小鼠比同窝对照小鼠更容易患急性结肠炎和实验诱导的 CAC。 Npm1 缺陷会损害产生白细胞介素 22 (IL-22) 的第三组先天淋巴细胞 (ILC3) 的功能。 ILC3 中缺乏 Npm1 的小鼠表现出 IL-22 产生减少并加速结肠炎的发展。 NPM1 通过 ILC3 中的氧化磷酸化对线粒体生物合成和代谢非常重要。进一步的实验表明，NPM1 与 p65 协同促进 ILC3 中线粒体转录因子 A (TFAM) 的转录。小鼠中 Npm1 的过度表达增强了 ILC3 功能并降低了葡聚糖硫酸钠诱导的结肠炎的严重程度。因此，我们的研究结果表明，ILC3 中的 NPM1 通过 p65-TFAM 轴调节线粒体代谢来预防 IBD。© 2024。作者。

Nucleophosmin 1 (NPM1) is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Concurrent inflammatory bowel diseases (IBD) and MDS are common, indicating a close relationship between IBD and MDS. Here we examined the function of NPM1 in IBD and colitis-associated colorectal cancer (CAC). NPM1 expression was reduced in patients with IBD. Npm1+/- mice were more susceptible to acute colitis and experimentally induced CAC than littermate controls. Npm1 deficiency impaired the function of interleukin-22 (IL-22)-producing group three innate lymphoid cells (ILC3s). Mice lacking Npm1 in ILC3s exhibited decreased IL-22 production and accelerated development of colitis. NPM1 was important for mitochondrial biogenesis and metabolism by oxidative phosphorylation in ILC3s. Further experiments revealed that NPM1 cooperates with p65 to promote mitochondrial transcription factor A (TFAM) transcription in ILC3s. Overexpression of Npm1 in mice enhanced ILC3 function and reduced the severity of dextran sulfate sodium-induced colitis. Thus, our findings indicate that NPM1 in ILC3s protects against IBD by regulating mitochondrial metabolism through a p65-TFAM axis.© 2024. The Author(s).