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

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

Science (New York, N.Y.) 2023 Sep 15

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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.

Citation

Yu Li, Shaorui Liu, Kewen Zhou, Yinsheng Wang, Yan Chen, Wen Hu, Shuyan Li, Hui Li, Yan Wang, Qiuying Wang, Danyang He, Heping Xu. Neuromedin U programs eosinophils to promote mucosal immunity of the small intestine. Science (New York, N.Y.). 2023 Sep 15;381(6663):1189-1196