Targeting the Aryl Hydrocarbon Receptor: The Potential of Indole Compounds in the Treatment of Cystic Fibrosis

Abstract

The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a crucial role in regulating immune homeostasis, inflammatory responses, and intestinal barrier function. Indole compounds and their derivatives are ligands of AHR, which can activate the AHR signal transduction pathway and show significant regulatory potential in various inflammatory and immune diseases. Cystic fibrosis (CF) is a life-threatening autosomal recessive genetic disorder. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects multiple systems throughout the body. The core of its pathological process is chronic infection, abnormal inflammation, and tissue damage caused by mucus accumulation. Exploring alternative or adjunctive therapeutic strategies targeting pathological pathways downstream of CFTR is of significant importance. The aim of the present study is to explore the multiple beneficial effects that indole compounds may exert in regulating pulmonary infection and inflammation, repairing intestinal barrier function, and regulating immune homeostasis in CF patients by activating the AHR signaling pathway. Additionally, this study discusses the risks and challenges associated with developing indole compounds as CF drugs, offering a novel research approach distinct from traditional CFTR modulators for creating new CF therapeutics.