Potent AhR agonist EQ504 facilitates gut epithelial repair in inflammatory disease models 4507

Abstract Description Aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that plays a critical role in regulating various cellular processes, including immune responses, barrier integrity, and cell differentiation. Epithelial cells, which form a protective barrier in tissues such as the gut, skin, and lungs, are highly responsive to environmental signals mediated by AhR. Herein, we describe a new potent small molecule agonist of AhR, EQ504, which exerts a protective effect on gut barrier healing and recovery. Caco-2 and T84 gut epithelial cell lines were cultured to form monolayers or plated on inserts for either a standard scratch assay to assess wound healing, or transepithelial electrical resistance (TEER) measurements to assess recovery of tight junctions. Cells were incubated with IFNg, TNFa and IL-1b or EDTA to activate inflammatory pathways and/or disrupt tight junctions, and treated with EQ504 or positive controls. Treatment with EQ504 significantly increased the time to scratch closure and accelerated the recovery of barrier function. EQ504 also induced upregulation of IL-10 expression, a key anti-inflammatory cytokine, thereby highlighting its potential as a therapeutic agent for managing intestinal inflammation and promoting mucosal recovery. These findings demonstrate the efficacy of EQ504 in promoting healing of gut epithelial cells from inflammation and damage, highlighting its potential therapeutic value for patients with inflammatory mucosal diseases. Topic Categories Mucosal and Regional Immunology (MUC)