title: The nuclear receptor LXRα controls the functional specialization of splenic macrophages.
abstract: Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols de Madrid, Consejo Superior de Investigaciones Cientificas-Universidad Autonóma de Madrid, Madrid, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: A-Gonzalez
authors.forename: Jose A
authors.initials: JA
authors.lastname: Guillen
authors.forename: Germán
authors.initials: G
authors.lastname: Gallardo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Diaz
authors.forename: Juan V
authors.initials: JV
authors.lastname: de la Rosa
authors.forename: Irene H
authors.initials: IH
authors.lastname: Hernandez
authors.forename: Maria
authors.initials: M
authors.lastname: Casanova-Acebes
authors.forename: Felix
authors.initials: F
authors.lastname: Lopez
authors.forename: Carlos
authors.initials: C
authors.lastname: Tabraue
authors.forename: Susana
authors.initials: S
authors.lastname: Beceiro
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hong
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Lara
authors.forename: Miguel
authors.initials: M
authors.lastname: Andujar
authors.forename: Satoko
authors.initials: S
authors.lastname: Arai
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Senlin
authors.initials: S
authors.lastname: Li
authors.forename: Angel L
authors.initials: AL
authors.lastname: Corbi
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.forename: Andres
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Antonio
authors.initials: A
authors.lastname: Castrillo
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007150:Immunohistochemistry; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology*
chemical_list: D001565:Benzoates; D001596:Benzylamines; C473027:GW 3965; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors