From TCDD-mediated toxicity to searches of physiologic AHR functions.

TCDD-mediated toxicity of human individuals together with animal studies led to identification of the aryl hydrocarbon receptor (AHR). It was characterized as multifunctional ligand-activated transcription factor and environmental sensor. Comparison of human toxic responses and animal models provide hints to physiologic AHR functions including chemical and microbial defense, homeostasis of stem/progenitor cells and modulation of the immune system in barrier organs such as skin and the gastrointestinal tract. Extrapolation from animals to humans is difficult due to marked species differences and dependence of AHR function on the cellular context. Nevertheless, therapeutic possibilities of AHR agonists and antagonists are in development. The AHR remains challenging and fascinating.