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Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier

Author

Listed:
  • Xiuchuan (Lucas) Hu

    (Fudan University
    King’s College London)

  • Wenfeng Xiao

    (Fudan University
    Fudan University)

  • Yuxian Lei

    (King’s College London)

  • Adam Green

    (King’s College London)

  • Xinyi Lee

    (King’s College London)

  • Muralidhara Rao Maradana

    (The Francis Crick Institute)

  • Yajing Gao

    (Fudan University
    Fudan University)

  • Xueru Xie

    (Fudan University
    Fudan University)

  • Rui Wang

    (King’s College London)

  • George Chennell

    (King’s College London)

  • M. Albert Basson

    (King’s College London
    University of Exeter Medical School)

  • Pete Kille

    (Cardiff University)

  • Wolfgang Maret

    (King’s College London)

  • Gavin A. Bewick

    (King’s College London)

  • Yufeng Zhou

    (Fudan University
    Fudan University)

  • Christer Hogstrand

    (King’s College London)

Abstract

Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether zinc and the AHR pathway are linked. We show that dietary supplementation with an AHR pre-ligand offers protection against inflammatory bowel disease in a mouse model while protection fails in mice lacking AHR in the intestinal epithelium. AHR agonist treatment is also ineffective in mice fed zinc depleted diet. In human ileum organoids and Caco-2 cells, AHR activation increases total cellular zinc and cytosolic free Zn2+ concentrations through transcription of genes for zinc importers. Tight junction proteins are upregulated through zinc inhibition of nuclear factor kappa-light-chain-enhancer and calpain activity. Our data show that AHR activation by plant-derived dietary ligands improves gut barrier function at least partly via zinc-dependent cellular pathways, suggesting that combined dietary supplementation with AHR ligands and zinc might be effective in preventing inflammatory gut disorders.

Suggested Citation

  • Xiuchuan (Lucas) Hu & Wenfeng Xiao & Yuxian Lei & Adam Green & Xinyi Lee & Muralidhara Rao Maradana & Yajing Gao & Xueru Xie & Rui Wang & George Chennell & M. Albert Basson & Pete Kille & Wolfgang Mar, 2023. "Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41168-y
    DOI: 10.1038/s41467-023-41168-y
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    References listed on IDEAS

    as
    1. Kathleen Shah & Muralidhara Rao Maradana & M. Joaquina Delàs & Amina Metidji & Frederike Graelmann & Miriam Llorian & Probir Chakravarty & Ying Li & Mauro Tolaini & Michael Shapiro & Gavin Kelly & Chr, 2022. "Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Teng Huang & Jia Song & Jia Gao & Jia Cheng & Hao Xie & Lu Zhang & Yu-Han Wang & Zhichao Gao & Yi Wang & Xiaohui Wang & Jinhan He & Shiwei Liu & Qilin Yu & Shu Zhang & Fei Xiong & Qing Zhou & Cong-Yi , 2022. "Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Chris Schiering & Emma Wincent & Amina Metidji & Andrea Iseppon & Ying Li & Alexandre J. Potocnik & Sara Omenetti & Colin J. Henderson & C. Roland Wolf & Daniel W. Nebert & Brigitta Stockinger, 2017. "Feedback control of AHR signalling regulates intestinal immunity," Nature, Nature, vol. 542(7640), pages 242-245, February.
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