Environmental Ligands of the Aryl Hydrocarbon Receptor in Allergic Rhinitis: Immune and Neuroimmune Mechanisms

Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated chronic inflammatory disease. Although type 2 immune responses are central to AR, environmental exposures, epithelial barrier dysfunction, and neuroimmune interactions also contribute to disease development. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that links environmental signals to immune responses. Elevated AhR expression in peripheral blood mononuclear cells from patients with AR has been associated with clinical severity. In non-AR experimental systems, AhR suppresses histamine-associated interleukin-6 (IL-6) production in macrophages, whereas 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces acetylcholinesterase (AChE) expression and activity in neuronal cells. These findings suggest possible links to nasal inflammation and cholinergic regulation, but their contribution to nasal symptoms in AR remains to be established. In addition, AhR modulates mast-cell, B-cell, and T-cell responses in a ligand- and cell-dependent manner. Overall, AhR may exert protective or pathogenic effects depending on the activating ligand and target cell type, suggesting that its therapeutic potential in AR lies in ligand- and cell-specific modulation.