{"title":"Tuft cells restrain intestinal type 2 immunity through the transcription factor Spi-B","authors":"Jiali Wang, Ruoxi Shen, Kunpeng Yang, Xiaohuan Guo, Jingyou Yu, Chuan Wu, Xue-Kun Guo, Xiaoyu Hu","doi":"10.1126/sciimmunol.ads5818","DOIUrl":null,"url":null,"abstract":"<div >Excessive type 2 immunity underlies various disease conditions, including allergies, yet the homeostatic mechanisms that limit type 2 responses are not fully understood. Here, we revealed that intestinal tuft cells, specialized epithelial cells known for triggering type 2 immune activation, also have a molecular circuit that restrains type 2 responses. Ablation of the transcription factor Spi-B in tuft cells was sufficient to elicit spontaneous type 2 inflammation. Tuft cell–intrinsic deficiency of Spi-B rendered otherwise resistant C57BL/6J mice susceptible to food allergy models. Spi-B repressed c-Kit signaling–driven production of the type 2 alarmin TSLP by tuft cells. Disruption of this negative regulatory axis led to tuft cell hyperplasia and exacerbated type 2 inflammation, which could be pharmacologically targeted with a tyrosine kinase inhibitor. These findings pinpoint a crucial tuft cell–centric checkpoint of type 2 immunity and highlight the dual role of tuft cells in both promoting and restraining type 2 responses.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 109","pages":""},"PeriodicalIF":17.6000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ads5818","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/sciimmunol.ads5818","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Excessive type 2 immunity underlies various disease conditions, including allergies, yet the homeostatic mechanisms that limit type 2 responses are not fully understood. Here, we revealed that intestinal tuft cells, specialized epithelial cells known for triggering type 2 immune activation, also have a molecular circuit that restrains type 2 responses. Ablation of the transcription factor Spi-B in tuft cells was sufficient to elicit spontaneous type 2 inflammation. Tuft cell–intrinsic deficiency of Spi-B rendered otherwise resistant C57BL/6J mice susceptible to food allergy models. Spi-B repressed c-Kit signaling–driven production of the type 2 alarmin TSLP by tuft cells. Disruption of this negative regulatory axis led to tuft cell hyperplasia and exacerbated type 2 inflammation, which could be pharmacologically targeted with a tyrosine kinase inhibitor. These findings pinpoint a crucial tuft cell–centric checkpoint of type 2 immunity and highlight the dual role of tuft cells in both promoting and restraining type 2 responses.
期刊介绍:
Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.