An overview of aryl hydrocarbon receptor ligands in the Last two decades (2002–2022): A medicinal chemistry perspective

Li, Lin; Dai, Yue; Xia, Yufeng

doi:10.1016/j.ejmech.2022.114845

Cited by 29 publications

(27 citation statements)

References 238 publications

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“…AhR-ARNT complex binding to the xenobiotic response element (XRE; also dioxin response element, DRE) in the target gene promotor region and its mediated gene expression is defined as the canonical AhR signaling ( 121 – 123 ). However, more recent studies demonstrated that AhR can interact with a variety of co-activators in a non-canonical signaling pathway, depending on the co-activator’s availability, and presumably the nature of the activating ligand ( 124 , 125 ). Therefore, all studies addressing the AhR function by activation or inhibition through specific ligands must be compared carefully to allow reliable conclusions.…”

Section: The Impact Of Nutrients On the Intestinal Epithelium And Iga...mentioning

confidence: 99%

Section: The Impact Of Nutrients On the Intestinal Epithelium And Iga...mentioning

confidence: 99%

“…Among the initially described toxic chemicals functioning as AhR ligands, a vast number of naturally occurring ( 126 ) and synthesized AhR agonists and antagonists have been described ( 125 , 127 ). The number of the latter is steadily increasing with the rising interest in AhR as a drug target in various diseases, including cancer, rheumatoid arthritis and inflammatory bowel disease ( 125 ). The interplay between the dietary composition, the variety of diet-derived AhR ligands generated by individual members of the intestinal microbiota or liver enzymes and the transport of these compounds through the organism to the site of action is incredibly complex and differs between individuals.…”

Section: The Impact Of Nutrients On the Intestinal Epithelium And Iga...mentioning

confidence: 99%

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The intestine: A highly dynamic microenvironment for IgA plasma cells

et al. 2023

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To achieve longevity, IgA plasma cells require a sophisticated anatomical microenvironment that provides cytokines, cell-cell contacts, and nutrients as well as metabolites. The intestinal epithelium harbors cells with distinct functions and represents an important defense line. Anti-microbial peptide-producing paneth cells, mucus-secreting goblet cells and antigen-transporting microfold (M) cells cooperate to build a protective barrier against pathogens. In addition, intestinal epithelial cells are instrumental in the transcytosis of IgA to the gut lumen, and support plasma cell survival by producing the cytokines APRIL and BAFF. Moreover, nutrients are sensed through specialized receptors such as the aryl hydrocarbon receptor (AhR) by both, intestinal epithelial cells and immune cells. However, the intestinal epithelium is highly dynamic with a high cellular turn-over rate and exposure to changing microbiota and nutritional factors. In this review, we discuss the spatial interplay of the intestinal epithelium with plasma cells and its potential contribution to IgA plasma cell generation, homing, and longevity. Moreover, we describe the impact of nutritional AhR ligands on intestinal epithelial cell-IgA plasma cell interaction. Finally, we introduce spatial transcriptomics as a new technology to address open questions in intestinal IgA plasma cell biology.

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Section: The Impact Of Nutrients On the Intestinal Epithelium And Iga...mentioning

confidence: 99%

Section: The Impact Of Nutrients On the Intestinal Epithelium And Iga...mentioning

confidence: 99%

Section: The Impact Of Nutrients On the Intestinal Epithelium And Iga...mentioning

confidence: 99%

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The intestine: A highly dynamic microenvironment for IgA plasma cells

et al. 2023

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“…A list of common AHR ligands, their abbreviations, whether they are exogenous or endogenous, whether they are synthetic or natural products, and their class and source Type Ligand Abbreviation Class Source References Exogenous synthetic ligands 2,3,7,8-Tetrachlorodibenzo-p-dioxin TCDD Agonists Municipal and industrial waste incineration, vehicle exhaust, PVC plastics, pesticide production, and steel smelting Kerkvliet N. I. 2012[ 328 ] Benzo[a]pyrene BaP Park R et al 2020; Großkopf, H et al 2021 [ 329 , 330 ] Benz(a)anthracene BA GMachala M et al 2001 [ 331 ] Polychlorinated biphenyls PCBs Safe S. H et al 2001[ 332 ] 4-(3-Chloro-phenyl)-pyrimidin-2-yl) -(4-trifluoromethyl-phenyl)-amine VAF347 Ibabao C. N et al 2015; Zapadka T. E et al 2021 [ 333 , 334 ] Natural exogenous ligands Berberine Berberine Agonists Dietary Vrzal R et al 2005 [ 95 ] 2-(indole-3-methane)-3, 3'-diindolylmethane LTr-1 Lin L et al 2022 [ 335 ] 3, 3-diindolylmethane DIM Chen I et al 1996 [ 336 ] Indolo[3,2-b] carbazole ICZ Esser C et al 2015[ 42 ] Flavonoids …”

Section: Ahr and Ligandsmentioning

confidence: 99%

Modulating AHR function offers exciting therapeutic potential in gut immunity and inflammation

Chen

Wang

et al. 2023

Cell Biosci

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Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a classical exogenous synthetic ligand of AHR that has significant immunotoxic effects. Activation of AHR has beneficial effects on intestinal immune responses, but inactivation or overactivation of AHR can lead to intestinal immune dysregulation and even intestinal diseases. Sustained potent activation of AHR by TCDD results in impairment of the intestinal epithelial barrier. However, currently, AHR research has been more focused on elucidating physiologic AHR function than on dioxin toxicity. The appropriate level of AHR activation plays a role in maintaining gut health and protecting against intestinal inflammation. Therefore, AHR offers a crucial target to modulate intestinal immunity and inflammation. Herein, we summarize our current understanding of the relationship between AHR and intestinal immunity, the ways in which AHR affects intestinal immunity and inflammation, the effects of AHR activity on intestinal immunity and inflammation, and the effect of dietary habits on intestinal health through AHR. Finally, we discuss the therapeutic role of AHR in maintaining gut homeostasis and relieving inflammation. Graphical Abstract

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“…Indeed, several endogenous AHR ligands have now been identified, including chemicals derived from tryptophan, phytochemicals, or commensal microbiota. 1 , 2 Although AHR might play many roles, no doubt it remains a critical receptor in modulating immune responses within the context of exposure to environmental chemicals.…”

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confidence: 99%