The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases
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...
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doaj-04ee09f417704fc2b83d640a28fcb6512020-11-25T00:14:40ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-12-011912385110.3390/ijms19123851ijms19123851The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory DiseasesDrew R. Neavin0Duan Liu1Balmiki Ray2Richard M. Weinshilboum3Mayo Clinic Graduate School of Biomedical Sciences, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55902, USADivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55902, USADivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55902, USADivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55902, USAThe 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.https://www.mdpi.com/1422-0067/19/12/3851aryl hydrocarbon receptor (AHR)single nucleotide polymorphisms (SNPs)tryptophan (TRP)aryl hydrocarbon response element (AHRE) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Drew R. Neavin Duan Liu Balmiki Ray Richard M. Weinshilboum |
spellingShingle |
Drew R. Neavin Duan Liu Balmiki Ray Richard M. Weinshilboum The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases International Journal of Molecular Sciences aryl hydrocarbon receptor (AHR) single nucleotide polymorphisms (SNPs) tryptophan (TRP) aryl hydrocarbon response element (AHRE) |
author_facet |
Drew R. Neavin Duan Liu Balmiki Ray Richard M. Weinshilboum |
author_sort |
Drew R. Neavin |
title |
The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases |
title_short |
The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases |
title_full |
The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases |
title_fullStr |
The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases |
title_full_unstemmed |
The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases |
title_sort |
role of the aryl hydrocarbon receptor (ahr) in immune and inflammatory diseases |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-12-01 |
description |
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. |
topic |
aryl hydrocarbon receptor (AHR) single nucleotide polymorphisms (SNPs) tryptophan (TRP) aryl hydrocarbon response element (AHRE) |
url |
https://www.mdpi.com/1422-0067/19/12/3851 |
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