Regional encoding of enteric nervous system responses to microbiota and type 2 inflammation

• 成果类型: Article
• 署名作者: Tan, Peng; Jaiswal, Alok; Murphy, Shane P.; Brown, Eric M.; Wheeler, Hailey; Su, Chien-Wen; Finan, Emily P.; Jasso, Guadalupe J.; Shi, Hai Ning; Graham, Daniel B.; Delorey, Toni M.; Deguine, Jacques; Xavier, Ramnik J.
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Hainan Medical University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adr3545
• 发表日期: 2025-10-30
• 页码: eadr3545
• 关键词: innate lymphoid-cells; gut microbiota; HEALTH; seq

摘要

Enteric neurons are essential regulators of intestinal physiology, yet their responses to varying microbial and immune environments along the intestinal tract and or during challenges remain poorly understood. In this study, we regionally profiled enteric neurons across gnotobiotic, allergic, and parasite-infected mice. Timing and complexity of microbial perturbations and type 2 inflammation result in motor neuron state shifts and alter multiple functionally distinct sensory neurons, including interleukin-13- and leukotriene-responsive Nmu-hi cells and Grp-hi neurons, which expand in germ-free colonic tissue and interact with Grpr+ interstitial cells of Cajal. Leveraging adeno-associated virus-based Perturb-seq, we identified Edf1 and Mitf as controllers of motor neuron state transition and gastrointestinal transit time, directly linking enteric neuron states to physiology.