The role of the aryl hydrocarbon receptor (AHR) in immune and inflammatory diseases

Drew R. Neavin, Duan Liu, Balmiki Ray, Richard M. Weinshilboum

Research output: Contribution to journalReview article

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number3851
JournalInternational journal of molecular sciences
Volume19
Issue number12
DOIs
StatePublished - Dec 2018

Keywords

  • Aryl hydrocarbon receptor (AHR)
  • Aryl hydrocarbon response element (AHRE)
  • Single nucleotide polymorphisms (SNPs)
  • Tryptophan (TRP)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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