Retinoid X receptors in macrophage biology

• RXRs have novel roles in physiological and pathological hematopoiesis.
• RXRs are key regulators of macrophage lipid metabolism and immune functions.
• RXRs have therapeutic potential in the treatment of metabolic and inflammatory diseases.
• Design of selective RXR modulators may overcome current limitations of RXR targeting in medicine.

Retinoid X receptors (RXRs) form a distinct and unique subclass within the nuclear receptor (NR) superfamily of ligand-dependent transcription factors. RXRs regulate a plethora of genetic programs, including cell differentiation, the immune response, and lipid and glucose metabolism. Recent advances reveal that RXRs are important regulators of macrophages, key players in inflammatory and metabolic disorders. This review outlines the versatility of RXR action in the control of macrophage gene transcription through its heterodimerization with other NRs or through RXR homodimerization. We also highlight the potential of RXR-controlled transcriptional programs as targets for the treatment of pathologies associated with altered macrophage function, such as atherosclerosis, insulin resistance, autoimmunity, and neurodegeneration.