西湖大学Heping Xu团队近期取得重要工作进展，他们研究发现，神经调节肽U编码嗜酸性粒细胞以促进小肠粘膜免疫。相关研究成果2023年9月15日在线发表于《科学》杂志上。

据介绍，嗜酸性粒细胞属于粒细胞系白细胞，在2型免疫中发挥重要作用，并调节小肠（SI）中多种稳态过程。然而，对于稳定状态下小肠中调节嗜酸性粒细胞活性的信号仍知之甚少。

通过对不同小鼠组织的嗜酸性粒细胞进行转录组分析，研究人员发现了小肠嗜酸性粒细胞的一个亚群表达神经调节U（NMU）受体1（NMUR1）。命运图谱分析表明，小肠嗜酸性粒细胞中的NMUR1表达由局部微环境编码，并通过炎症进一步增强。遗传扰动和嗜酸性粒细胞-类器官共培养实验表明，NMU介导的嗜酸性粒细胞活化可促进杯状细胞分化。

因此，NMU通过刺激SI中表达NMUR1的嗜酸性粒细胞来调节上皮细胞分化和屏障免疫，这突出了神经免疫和上皮细胞相互作用在维持组织稳态中的重要性。

附：英文全文

Title: Neuromedin U programs eosinophils to promote mucosal immunity of the small intestine

Author: Yu Li, Shaorui Liu, Kewen Zhou, Yinsheng Wang, Yan Chen, Wen Hu, Shuyan Li, Hui Li, Yan Wang, Qiuying Wang, Danyang He, Heping Xu

Issue&Volume: 2023-09-15

Abstract: Eosinophils are granulocytes that play an essential role in type 2 immunity and regulate multiple homeostatic processes in the small intestine (SI). However, the signals that regulate eosinophil activity in the SI at steady state remain poorly understood. Through transcriptome profiling of eosinophils from various mouse tissues, we found that a subset of SI eosinophils expressed neuromedin U (NMU) receptor 1 (NMUR1). Fate-mapping analyses showed that NMUR1 expression in SI eosinophils was programmed by the local microenvironment and further enhanced by inflammation. Genetic perturbation and eosinophil-organoid coculture experiments revealed that NMU-mediated eosinophil activation promotes goblet cell differentiation. Thus, NMU regulates epithelial cell differentiation and barrier immunity by stimulating NMUR1-expressing eosinophils in the SI, which highlights the importance of neuroimmune-epithelial cross-talk in maintaining tissue homeostasis.

DOI: ade4177

Source: https://www.science.org/doi/10.1126/science.ade4177