Targeting the Aryl Hydrocarbon Receptor to Attenuate IGF1R Signaling in Thyroid Eye Disease

Background: Thyroid eye disease (TED) is an autoimmune disorder characterized by proptosis, inflammation, and fibrosis. Elevated insulin-like growth factor 1 receptor (IGF1R) signaling in TED orbital fibroblasts (OFs) drives the proliferation and biosynthesis of hyaluronan, which causes enlargement of orbital tissue volume. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular stress responses, metabolism, and inflammation. Given its important role in regulating cellular responses, we hypothesized that activation of the AHR could limit excessive IGF1R signaling in TED OFs, offering therapeutic potential.