Aryl Hydrocarbon Receptor in Health and Disease

The aryl hydrocarbon receptor (AhR) functions as a ligand-dependent transcription factor, serving as a pivotal environmental sensor that significantly influences both physiological and pathological processes. The inactivated state of AhR is present in the cell cytoplasm and transfer into the nucleus upon activation by a variety of ligands. It subsequently regulates a variety of processes including cellular metabolism, organ and tissue development, and maintenance of immune homeostasis. Despite substantial advancements over the past decade, the mechanisms by which AhR specifically regulates immune cell function in response to environmental factors and influences disease progression remain not fully elucidated. This review systematically analyzes the basic structure and major signaling pathways of AhR, its physiological functions in maintaining organismal homeostasis and its mechanism of action on various types of immune cells, and their therapeutic potential in autoimmune diseases, inflammatory disorders, tumor microenvironment, and neurodegenerative diseases. Translating immune-metabolic reprogramming mechanisms into clinical applications represents a pivotal challenge in AhR research. And this review integrates and analyzes the great potential of AhR as a pleiotropic therapeutic target for regulating immunity and treating a series of diseases, offering actionable frameworks for future exploration.