Aryl hydrocarbon receptor (AHR): From selected human target genes and crosstalk with transcription factors to multiple AHR functions

Accumulating evidence including studies of AHR-deficient mice and TCDD toxicity suggests multiple physiologic AHR functions. Challenges to identify responsible mechanisms are due to marked species differences and dependence upon cell type and cellular context. Transient AHR modulation is often necessary for physiologic functions whereas TCDD-mediated sustained receptor activation has been demonstrated to be responsible for toxic outcomes. To stimulate studies on responsible action mechanisms the commentary is focused on human AHR target genes and crosstalk with transcription factors. Discussed AHR functions include chemical and microbial defense, organ development, modulation of immunity and inflammation, reproduction, and NAD(+)-dependent energy metabolism. Obviously, much more work is needed to elucidate action mechanisms. In particular, studies of pathways leading to NAD(+)-dependent energy metabolism may shed light on the puzzling species differences of TCDD-mediated lethality and provide options for treatment of obesity and age-related degenerative diseases.