Tuft cells restrain intestinal type 2 immunity through the transcription factor Spi-B

IF 17.6 1区 医学 Q1 IMMUNOLOGY
Jiali Wang, Ruoxi Shen, Kunpeng Yang, Xiaohuan Guo, Jingyou Yu, Chuan Wu, Xue-Kun Guo, Xiaoyu Hu
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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.

Abstract Image

簇毛细胞通过转录因子Spi-B抑制肠道2型免疫
过多的2型免疫是多种疾病的基础,包括过敏,但限制2型反应的稳态机制尚不完全清楚。在这里,我们揭示了肠簇细胞,已知的触发2型免疫激活的特化上皮细胞,也有一个抑制2型免疫反应的分子电路。簇状细胞中转录因子Spi-B的消融足以引发自发性2型炎症。簇状细胞内禀缺乏Spi-B使其他耐药的C57BL/6J小鼠对食物过敏模型敏感。Spi-B抑制簇状细胞c-Kit信号驱动的2型警报蛋白TSLP的产生。这种负调节轴的破坏导致簇状细胞增生和2型炎症加剧,这可能是酪氨酸激酶抑制剂的药理学靶点。这些发现指出了一个关键的簇状细胞为中心的2型免疫检查点,并强调了簇状细胞在促进和抑制2型应答中的双重作用。
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来源期刊
Science Immunology
Science Immunology Immunology and Microbiology-Immunology
CiteScore
32.90
自引率
2.00%
发文量
183
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.
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