Aryl Hydrocarbon Receptor (AhR)

The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in modulating intestinal immune responses (1). AhR induces its negative regulator, the AHR repressor (AHRR), which is vital for sustaining intestinal intraepithelial lymphocytes (IELs) (1).

References:
(1) Panda et al. 2023 Immunity 56(4): 797-812

The aryl hydrocarbon receptor acts as a mediator in the interaction between the host and microbiota.
Dong & Perdew 2020 Gut Microbes 12: 1859812

Situated in the cytoplasm in an inactive complex, Aryl Hydrocarbon Receptor (AhR) translocates into the nucleus upon ligand binding and recognizes promoters containing specific enhancer sequences termed Xenobiotic Responsive Elements (XREs), inducing de novo transcription of multiple target genes
Lee et al. 2011a Nat. Immunol. 13: 144–151

The AhR is a ligand-activated transcription factor and protein-binding partner originally recognized for its activation by environmental chemicals including 2,3,7,8-Tetrachlorodibenzodioxin (TCDD), Polychlorinated biphenyls (PCBs), and Polycyclic aromatic hydrocarbon (PAH). AhR activation induces expression of CYP1A1, CYP1A2, and CYP1B1 monoxygenases capable of metabolizing some environmental AhR ligands, including PAH common in cigarette smoke, into mutagenic intermediates.
Gu et al. 2000 Annu Rev Pharmacol Toxicol 40: 519-561

Smoke-derived mutagens have been linked to lung adenocarcinoma (LUAD) and various other cancers for a long time.
Tsay et al. 2013 Anticancer Res 33: 1247-1256
Holme et al. 2023 Biochem Pharmacol 216: 115801

The activation of the AhR, regardless of the method, is linked to immunosuppression in various contexts. The interaction between kynurenine and the aryl hydrocarbon receptor results in the generation of regulatory T cells. The blockade of the AHR limits a suppressive axis between Treg and macrophages that is induced by L-Kynurenine.
Mezrich et al. 2010 J Immunol 185: 3190-3198
Quintana 2013 Semin Immunopathol 35: 627-635
Quintana & Sherr 2013 Pharmacol Rev 65: 1148-1161
Bruhs et al. 2015 J. Investig. Dermatol. 135: 435-444
Campesato et al. 2020 Nat Commun 11: 4011

Activation of AhR by agonist binding and the transcriptional activation of genes are involved in the metabolism of xenobiotics
Schmidt & Bradfield 1996 Annu Rev. Cell Dev. Biol. 12: 55–89

Genetic Deficiency and Intestinal Health

Genetic deficiency in Aryl Hydrocarbon Receptor (AhR) is associated with compromised intestinal barrier integrity, altered microbiota composition, and dysregulated host responses to pathogens and injury (1, 2 3, 4 ).The enteric neuron-specific deletion of AhR, a microbiota-dependent gene, negatively affects intestinal motility, highlighting AhR's role as a potential biosensor in ENS neurons (5).

References:
(1) Kiss et al. 2011 Science. 334: 1561–1565
(2) Li et al. 2011 Cell 147: 629–640
(3) Schiering et al. 2017 Nature 542: 242-245
(4) Shah et al. 2022 Nat. Commun. 13: 1827
(5) Obata et al. 2020 Nature 578: 284-289

Aryl Hydrocarbon Receptor (AhR) deficiency increases epithelial immunopathology
Li et al. 2011 Cell 147: 629–640

see also:
AhR signal transduction pathway
Dioxins