Dietary nucleic acids promote oral tolerance through innate sensing pathways in mice

Tao Yang, Tian Li, Yingying Xing, Mengtao Cao, Mingxiang Zhang, Qibin Leng, Ju Qiu, Xinyang Song, Jianfeng Chen, Guohong Hu and Youcun Qian ()
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Tao Yang: Chinese Academy of Sciences
Tian Li: Chinese Academy of Sciences
Yingying Xing: Chinese Academy of Sciences
Mengtao Cao: Chinese Academy of Sciences
Mingxiang Zhang: ShanghaiTech University
Qibin Leng: State Key Laboratory of Respiratory Disease
Ju Qiu: Chinese Academy of Sciences
Xinyang Song: University of Chinese Academy of Sciences
Jianfeng Chen: University of Chinese Academy of Sciences
Guohong Hu: Chinese Academy of Sciences
Youcun Qian: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Oral tolerance is essential for intestinal homeostasis and systemic immune function. However, our understanding of how oral tolerance is maintained is inadequate. Here we report that food-derived nucleic acids promote oral tolerance through innate sensing pathways. We find that dietary nucleic acids, but not microbiota, expand the natural intraepithelial lymphocyte (IEL) pool, specifically in the small intestine. TGF-β1, produced by natural IELs, then promotes activation of gut CD103+ dendritic cells to support the induction of antigen-specific Treg cells in a mouse model of OVA-induced oral tolerance. Mechanistically, MAVS and STING are redundantly required for sensing dietary RNAs and DNAs to activate downstream TBK1 signalling to induce IL-15 production, which results in the accumulation of natural IELs. Thus, our study demonstrates a key role of food-triggered innate sensing pathways in the maintenance of natural IELs and oral tolerance.

Date: 2024
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DOI: 10.1038/s41467-024-53814-0

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