RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization

Retinoic acid receptor-related orphan receptor-α (RORα), a nuclear receptor transcription factor, is essential for maintaining organismal homeostasis and regulating diverse physio-pathological processes. However, its emerging role as a molecular nexus that integrates cholesterol metabolism with macrophage polarization to promote metabolic inflammation has not been systematically summarized. Cholesterol synthesis, transport, and efflux are critical for macrophage polarization. RORα regulates key components of these metabolic pathways and the associated transcriptional mechanisms driving polarization. Moreover, RORα regulates various other immune cells, such as T cells and microglia. This review aims to elucidate the core mechanisms of RORα in the crosstalk between cholesterol metabolism and inflammation, providing a novel method for therapeutic strategies.