中国科学院苏州医工所孙敏轩等研究人员合作发现，核仁磷酸蛋白1通过支持线粒体氧化磷酸化和ILC3活性促进粘膜免疫。2024年8月5日，《自然—免疫学》杂志在线发表了这项成果。

研究人员表示，核仁磷酸蛋白1（NPM1）在骨髓增生异常综合症（MDS）和急性髓系白血病中常见突变。共病的炎症性肠病（IBD）和MDS很常见，表明IBD与MDS之间存在密切关系。

研究人员检查了NPM1在IBD和结肠炎相关结直肠癌（CAC）中的功能。IBD患者的NPM1表达降低。Npm1+/−小鼠对急性结肠炎和实验诱导的CAC的易感性高于对照组。Npm1缺失损害了产生白介素-22（IL-22）的三型先天淋巴细胞（ILC3）的功能。缺失Npm1的ILC3小鼠表现出IL-22产生减少和结肠炎发展加速。NPM1在ILC3中通过氧化磷酸化对线粒体生物发生和代谢至关重要。

进一步实验显示，NPM1与p65合作，促进ILC3中线粒体转录因子A（TFAM）的转录。Npm1在小鼠中过表达增强了ILC3功能，并减少了硫酸钠引起的结肠炎的严重性。因此，这些研究结果表明，ILC3中的NPM1通过p65-TFAM轴调节线粒体代谢，从而保护免受IBD的影响。

附：英文原文

Title: Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity

Author: Zhao, Rongchuan, Yang, Jiao, Zhai, Yunjiao, Zhang, Hong, Zhou, Yuanshuai, Hong, Lei, Yuan, Detian, Xia, Ruilong, Liu, Yanxiang, Pan, Jinlin, Shafi, Shaheryar, Shi, Guohua, Zhang, Ruobing, Luo, Dingsan, Yuan, Jinyun, Pan, Dejing, Peng, Changgeng, Li, Shiyang, Sun, Minxuan

Issue&Volume: 2024-08-05

Abstract: 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.

DOI: 10.1038/s41590-024-01921-x

Source: https://www.nature.com/articles/s41590-024-01921-x

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