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The Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor belonging to the basic helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) family (UniProt: P35869). Originally identified for its role in sensing and detoxifying environmental pollutants like dioxins, AhR is now recognized as a critical regulator of physiological processes including immune homeostasis, vascular development, and cell cycle progression (PubMed: 29107552). Upon ligand binding in the cytoplasm, AhR translocates to the nucleus where it forms a heterodimer with the Aryl hydrocarbon receptor nuclear translocator (ARNT). This complex binds to specific DNA sequences known as Xenobiotic Response Elements (XRE) to induce the transcription of target genes, most notably the cytochrome P450 family, such as CYP1A1 (NCBI Gene: 196). In modern drug development, AhR is targeted for its immunomodulatory properties in treating autoimmune and inflammatory skin conditions, such as psoriasis and atopic dermatitis, as well as its potential role in the tumor microenvironment where it often promotes immune evasion (PubMed: 30116051). Therapeutic strategies include the use of Selective Aryl Hydrocarbon Receptor Modulators (SAhRMs) to achieve tissue-specific effects while minimizing systemic toxicity (PubMed: 25533383).
Ligand binding induces translocation to the nucleus, dimerization with ARNT, and binding to Xenobiotic Response Elements (XRE) to modulate gene transcription.
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