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.
Highlights
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that was first identified as a result of its role in modulating the response to exogenous chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—a contaminant of the chemical herbicide Agent Orange
We have recently demonstrated that AHR is associated with inter-individual variation in the plasma KYN concentration in major depressive disorder (MDD) patients and that variation in the KYN concentration was associated with MDD severity
Murine models exposed to AHR ligands such as BaP or TCDD resulted in increased atherosclerosis
Summary
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that was first identified as a result of its role in modulating the response to exogenous chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—a contaminant of the chemical herbicide Agent Orange. Elucidation of the role of AHR in disease and health is crucial to understand inter-individual variation in disease prevalence and therapeutic response and may aid in the development of novel therapies [12]. AHR plays an important role in the response to both gram-negative and gram-positive pathogens and understanding these mechanisms may make it possible to identify novel therapeutic agents that can be used to combat microbial pathogens
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
