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

Hu, Xiuchuan (Lucas), Xiao, Wenfeng, Lei, Yuxian, Green, Adam, Lee, Xinyi, Maradana, Muralidhara Rao, Gao, Yajing, Xie, Xueru, Wang, Rui, Chennell, George, Basson, M. Albert, Kille, Pete ORCID: https://orcid.org/0000-0001-6023-5221, Maret, Wolfgang, Bewick, Gavin A., Zhou, Yufeng and Hogstrand, Christer 2023. Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier. Nature Communications 14 , 5431. 10.1038/s41467-023-41168-y

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	7 September 2023
Date of Acceptance:	21 August 2023
Last Modified:	08 Sep 2023 02:09
URI:	https://orca.cardiff.ac.uk/id/eprint/162302

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