Aryl hydrocarbon receptor

Figures & data

Figure 1. Aryl Hydrocarbon Receptor (AhR) activity in RORγt⁺ ILC is essential for the first step of lymphoid follicle formation in the gut. Intestinal lymphoid follicles such as cryptopatches (CP) appear early after birth via the recruitment and the expansion of RORγt⁺ ILC at site. This step is independent of the presence of the indigenous microbiota in the gut. After CP development, invading microbiota drives some of them to further evolve into isolated lymphoid follicles (ILF) via the recruitment of plasma cells. Importantly, RORγt⁺ ILC expansion seems to be dependent on external factors such as nutrients. RORγt⁺ ILC, in particular the CD4-negative cell subset, are able to sense variation in phytochemical compound in the diet via the AhR. Activation of AhR induces upregulation of Kit and potentially Notch2 and IL-7R on RORγt⁺ ILC, supporting their maintenance. In Ahr-deficient mice, CD4^- RORγt⁺ ILC cannot survive and expand leading to a lack of intestinal lymphoid follicle formation.

Table 1. Representative AhR ligands

Synthetic ligands
Halogenated aromatic hydrocarbons (HAH)	2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
	2,3,7,8-Tetrachlorodibenzofuran
	3,3′,4,4'-Tetrachloroazoxybenzene
	2,3,6,7-Tetrachloronaphthalene
Polychlorinated Biphenyls (PCB)	3,3′,4,4',5-Pentachlorobiphenyl
Polycyclic aromatic hydrocarbons (PAH)	3-Methylcholanthrene
	Benzo[a]pyrene
Endogenous ligands
Tryptophan derivatives	Indigo
	Indirubin
	Tryptamine
	6-Formylindolo[3,2-b]carbazole (FICZ)
	Indole acetic acid (IAA)
	2-(1'H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE)
Tetrapyrroles	Bilirubin
Arachidonic acid metabolites	Lipoxin A4
	Prostaglandin G
Estrogens	Equilenin
Lipoproteins	Modified low-density lipoprotein
Dietary ligands
Flavonoids	Quercetin
	Genistein
	Daidzein
Phenolic acids	Curcumin
Stilbenoids	Resveratrol
Indole-3-carbinol derivatives	Indolo[3,2-b]carbazole (ICZ)
	3,3′-Diindolylmethane (DIM)

AhR ligands can be divided into synthetic ligands, endogenous ligands and natural dietary ligands. Table shows classes of compounds with specific examples, known to activate AhR. Adapted from reviews by Denison and Nagy, 2003⁴¹ and Nguyen and Bradfield, 2008.¹³

Denison MS, Nagy SR. Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 2003; 43:309 - 34; http://dx.doi.org/10.1146/annurev.pharmtox.43.100901.135828; PMID: 12540743

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Nguyen LP, Bradfield CA. The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol 2008; 21:102 - 16; http://dx.doi.org/10.1021/tx7001965; PMID: 18076143

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