嗜酸性粒细胞是颗粒细胞中的一类，在2型免疫反应中起着重要作用，并在小肠中调节多种体内稳态过程。然而，小肠内嗜酸性粒细胞活性的调节机制在稳定状态下仍不清楚。通过对不同小鼠组织中嗜酸性粒细胞的转录组分析，我们发现部分小肠嗜酸性粒细胞表达神经调质U受体1（NMUR1）。命运映射分析显示，小肠嗜酸性粒细胞中的NMUR1表达由局部微环境编程，并在炎症作用下进一步增强。遗传扰动和嗜酸性粒细胞-器官样培养实验结果显示，NMU介导的嗜酸性粒细胞激活能促进腺细胞分化。因此，NMU通过刺激小肠中表达NMUR1的嗜酸性粒细胞，调控上皮细胞分化和屏障免疫功能，突显了神经免疫-上皮细胞间相互作用在维持组织稳态中的重要性。

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.