Retinoid X receptor α controls innate inflammatory responses through the up-regulation of chemokine expression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 23; pp. 10626 - 10631
• Main Authors: Núñez, Vanessa, Alameda, Daniel, Rico, Daniel, Mota, Rubén, Gonzalo, Pilar, Cedenilla, Marta, Fischer, Thierry, Boscá, Lisardo, Glass, Christopher K., Arroyo, Alicia G., Ricote, Mercedes, Steinberg, Daniel
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.06.2010; National Acad Sciences
• Subjects: Animals; Base Sequence; Biological Sciences; Cells, Cultured; Chemokines; Chemokines, CC - genetics; Chemokines, CC - immunology; Immunity, Innate; Inflammation; Leukocytes; Ligands; Macrophage Inflammatory Proteins - genetics; Macrophage Inflammatory Proteins - immunology; Macrophages; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Knockout; Nuclear receptors; Receptors; Retinoid X Receptor alpha - deficiency; Retinoid X Receptor alpha - immunology; Retinoids; Sepsis; Sepsis - genetics; Sepsis - immunology; Sepsis - metabolism; Sepsis - therapy; Transcription, Genetic; Up-Regulation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0913545107

The retinoid X receptor α (RXRα) plays a central role in the regulation of many intracellular receptor signaling pathways and can mediate ligand-dependent transcription by forming homodimers or heterodimers with other nuclear receptors. Although several members of the nuclear hormone receptor superfamily have emerged as important regulators of macrophage gene expression, the existence in vivo of an RXR signaling pathway in macrophages has not been established. Here, we provide evidence that RXRα regulates the transcription of the chemokines Cd6 and Cd9 in macrophages independently of heterodimeric partners. Mice lacking RXRα in myeloid cells exhibit reduced levels of CCL6 and CCL9, impaired recruitment of leukocytes to sites of inflammation, and lower susceptibility to sepsis. These studies demonstrate that macrophage RXRα plays key roles in the regulation of innate immunity and represents a potential target for immunotherapy of sepsis.