AHR in the skin: From the mediator of chloracne to a therapeutic panacea?

The transcription factor AHR is highly expressed in all skin cells and an increasing body of evidence shows its involvement in immunity of barrier organds. The AHR is activated by many molecules found in the environment, both man-made and natural compounds, e.g., from dietary plants. Also endogenous activators of AHR were identified. We here review beneficial and adverse functions of activated AHR for skin integrity and skin health. We identify open questions, and hypothesize how concurrent inflammatory events can influence the outcome of physiological AHR signaling in the skin. AHR is a highly interesting therapeutic target, but different ligands can result in completely different immune effects. The underlying reasons, such as possible differences in ligand-induced conformational changes, are often unclear or speculative. This remains a challenge for therapeutic use. Also, long-term effects such as epigenetic changes need to come more into focus.