Neuromedin U programs eosinophils to promote mucosal immunity of the small intestine-Reference-Cited by-同舟云学术

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

Published:2023-09-15 Issue:6663 Volume:381 Page:1189-1196
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Li Yu¹²³⁴^ORCID,Liu Shaorui²³⁴^ORCID,Zhou Kewen²³⁴^ORCID,Wang Yinsheng²³⁴,Chen Yan⁵^ORCID,Hu Wen⁶^ORCID,Li Shuyan⁷,Li Hui²³⁴^ORCID,Wang Yan²³⁴,Wang Qiuying²³⁴^ORCID,He Danyang²³^ORCID,Xu Heping²³⁴^ORCID

Affiliation:

1. School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang, China.

2. Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China.

3. Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China.

4. Laboratory of Systems Immunology, Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang, China.

5. Center for Inflammatory Bowel Diseases, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.

6. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China.

7. Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

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

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