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

Author

Listed:
  • 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
    ShanghaiTech University)

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.

Suggested Citation

  • Tao Yang & Tian Li & Yingying Xing & Mengtao Cao & Mingxiang Zhang & Qibin Leng & Ju Qiu & Xinyang Song & Jianfeng Chen & Guohong Hu & Youcun Qian, 2024. "Dietary nucleic acids promote oral tolerance through innate sensing pathways in mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53814-0
    DOI: 10.1038/s41467-024-53814-0
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    1. Mahima Swamy & Lucie Abeler-Dörner & James Chettle & Tanel Mahlakõiv & Delphine Goubau & Probir Chakravarty & George Ramsay & Caetano Reis e Sousa & Peter Staeheli & Barbara A. Blacklaws & Jonathan L., 2015. "Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
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