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The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases

1
Mayo Clinic Graduate School of Biomedical Sciences, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55902, USA
2
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55902, USA
*
Author to whom correspondence should be addressed.
Present affiliation: Assurex Health Inc., Mason, OH 45040, USA.
Int. J. Mol. Sci. 2018, 19(12), 3851; https://doi.org/10.3390/ijms19123851
Received: 24 October 2018 / Revised: 27 November 2018 / Accepted: 29 November 2018 / Published: 3 December 2018
(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology)
The aryl hydrocarbon receptor (AHR) is a nuclear receptor that modulates the response to environmental stimuli. It was recognized historically for its role in toxicology but, in recent decades, it has been increasingly recognized as an important modulator of disease—especially for its role in modulating immune and inflammatory responses. AHR has been implicated in many diseases that are driven by immune/inflammatory processes, including major depressive disorder, multiple sclerosis, rheumatoid arthritis, asthma, and allergic responses, among others. The mechanisms by which AHR has been suggested to impact immune/inflammatory diseases include targeted gene expression and altered immune differentiation. It has been suggested that single nucleotide polymorphisms (SNPs) that are near AHR-regulated genes may contribute to AHR-dependent disease mechanisms/pathways. Further, we have found that SNPs that are outside of nuclear receptor binding sites (i.e., outside of AHR response elements (AHREs)) may contribute to AHR-dependent gene regulation in a SNP- and ligand-dependent manner. This review will discuss the evidence and mechanisms of AHR contributions to immune/inflammatory diseases and will consider the possibility that SNPs that are outside of AHR binding sites might contribute to AHR ligand-dependent inter-individual variation in disease pathophysiology and response to pharmacotherapeutics. View Full-Text
Keywords: aryl hydrocarbon receptor (AHR); single nucleotide polymorphisms (SNPs); tryptophan (TRP); aryl hydrocarbon response element (AHRE) aryl hydrocarbon receptor (AHR); single nucleotide polymorphisms (SNPs); tryptophan (TRP); aryl hydrocarbon response element (AHRE)
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Neavin, D.R.; Liu, D.; Ray, B.; Weinshilboum, R.M. The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases. Int. J. Mol. Sci. 2018, 19, 3851.

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