title: Retinoid X receptor alpha controls innate inflammatory responses through the up-regulation of chemokine expression.
abstract: The retinoid X receptor alpha (RXRalpha) 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 RXRalpha regulates the transcription of the chemokines Ccl6 and Ccl9 in macrophages independently of heterodimeric partners. Mice lacking RXRalpha 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 RXRalpha plays key roles in the regulation of innate immunity and represents a potential target for immunotherapy of sepsis.
authors.affiliation: Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Núñez
authors.forename: Daniel
authors.initials: D
authors.lastname: Alameda
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.forename: Rubén
authors.initials: R
authors.lastname: Mota
authors.forename: Pilar
authors.initials: P
authors.lastname: Gonzalo
authors.forename: Marta
authors.initials: M
authors.lastname: Cedenilla
authors.forename: Thierry
authors.initials: T
authors.lastname: Fischer
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.forename: Alicia G
authors.initials: AG
authors.lastname: Arroyo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ricote
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D047490:Retinoid X Receptor alpha / Q000172:deficiency / Q000276:immunology*; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C095218:Ccl9 protein, mouse; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D047490:Retinoid X Receptor alpha; C070959:Ccl6 protein, mouse