ILC3s promote intestinal tuft cell hyperplasia and anthelmintic immunity through RANK signaling

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2025-05-16 DOI:10.1126/sciimmunol.adn1491

Hongkai Xu, Yibo Wang, Wenyan Wang, Yang-Xin Fu, Ju Qiu, Yan Shi, Lei Yuan, Chen Dong, Xiaoyu Hu, Ye-Guang Chen, Xiaohuan Guo

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Abstract

Helminth infections, particularly in developing countries, remain a notable health burden worldwide. Group 3 innate lymphoid cells (ILC3s) are enriched in the intestine and play a critical role in immunity against extracellular bacteria and fungi. However, whether ILC3s are involved in intestinal helminth infection is still unclear. Here, we report that helminth infection reprograms ILC3s, which, in turn, promote anthelmintic immunity. ILC3-derived RANKL [receptor activator of NF-κB (nuclear factor κB) ligand] synergizes with interleukin-13 (IL-13) to facilitate intestinal tuft cell expansion after helminth infection, which further activates the tuft cell–group 2 innate lymphoid cell (ILC2) circuit to control helminth infection. Deletion of RANKL in ILC3s or deletion of RANK or its downstream adaptor RelB in intestinal epithelial cells substantially diminishes tuft cell hyperplasia and dampens anthelmintic immunity. Thus, ILC3s play an indispensable role in protecting against helminth infection through the regulation of intestinal tuft cell hyperplasia and type 2 immunity.

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ILC3s通过RANK信号通路促进肠簇细胞增生和驱虫免疫

寄生虫感染，特别是在发展中国家，仍然是世界范围内一个显著的健康负担。3组先天淋巴样细胞（ILC3s）在肠道中富集，在抵抗细胞外细菌和真菌的免疫中起关键作用。然而，ILC3s是否参与肠蠕虫感染尚不清楚。在这里，我们报道了蠕虫感染重新编程ILC3s，这反过来又促进了对寄生虫的免疫。ilc3衍生的RANKL [NF-κB（核因子κB）配体受体激活因子]与白细胞介素-13 （IL-13）协同作用，促进蠕虫感染后肠道簇状细胞扩增，进而激活簇状细胞- 2群先天淋巴样细胞（ILC2）回路，控制蠕虫感染。ILC3s中RANKL的缺失或肠上皮细胞中RANK或其下游接头RelB的缺失可显著减少簇状细胞增生并抑制驱虫免疫。因此，ILC3s通过调节肠簇细胞增生和2型免疫，在预防蠕虫感染中发挥着不可或缺的作用。

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来源期刊

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.