AhR

The Aryl hydrocarbon Receptor(AhR) is a member of the bHLH-PAS family, and it is a highly conserved nuclear receptor that regulates gene expression after ligand binding. As a nuclear receptor, AHR is bound by cochaperones that maintain its localization in the cytoplasm. However, following ligand binding, AHR is released by the cochaperones and is transported into the nucleus, where it heterodimerizes with the aryl hydrocarbon receptor nuclear translocator (ARNT).  One of the key target genes activated in the AhR genomic pathway is the AhR repressor, AhRR . The AhRR protein is similar to the AhR but it cannot bind ligands due to the absence of the PAS B domain in the N-terminal region. Further, the AhRR differs from AhR and ARNT in that the C-terminal domain, which is a transactivation domain in AhR and ARNT, is a transrepression domain in AhRR.  
AHR regulates the expression and activation of indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase (TDO2), kynureninase (KYNU), and kynurenine 3-monooxygenase (KMO), which are enzymes that regulate the kynurenine (KYN) arm of TRP metabolism, thereby providing a feedback loop since KYN is an agonist for AHR.AHR has been shown to play an important role in modulating the response to many microbial pathogens. the role of AHR is model-specific, disease phenotype-specific, and ligand-specific, with AHR activation contributing to the symptoms of some diseases, but relieving the symptoms of other diseases and in some cases (i.e., RA and MS) the result and effect of AHR activation is dependent on the ligand. AHR ligands, including AHR agonists, and selective AHR modulators (SARMs), have been suggested as potentially safe and effective therapeutic treatments that may be useful for the treatment of immune and inflammatory disease phenotypes that are regulated by AHR.

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1.Lucie Larigot, et al. Biochim Open. 2018 Dec; 7: 1–9.
2.Drew R. Neavin, et al. Int J Mol Sci. 2018 Dec; 19(12): 3851.