Using the Key Characteristics Framework to Unlock the Mysteries of Aryl Hydrocarbon Receptor–Mediated Effects on the Immune System

Initially discovered for its role mediating the deleterious effects of environmental contaminants, the aryl hydrocarbon receptor (AHR) is now known to be a crucial regulator of the immune system. The expanding list of AHR ligands includes synthetic and naturally derived molecules spanning pollutants, phytochemicals, pharmaceuticals, and substances derived from amino acids and microorganisms. The consequences of engaging AHR vary, depending on factors such as the AHR ligand, cell type, immune challenge, developmental state, dose, and timing of exposure relative to the immune stimulus. This review frames this complexity using the recently identified key characteristics of agents that affect immune system function (altered cell signaling, proliferation, differentiation, effector function, communication, trafficking, death, antigen presentation and processing, and tolerance). The use of these key characteristics provides a scaffold for continued discovery of how AHR and its myriad ligands influence the immune system, which will help harness the power of this enigmatic receptor to prevent or treat disease.