title: MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis.
abstract: Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, whereas the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. We now report that knockdown of MAFB impairs the acquisition of the anti-inflammatory profile of human macrophages, identify the MAFB-dependent gene signature in human macrophages and illustrate the coexpression of MAFB and MAFB-target genes in CD163+tissue-resident and tumor-associated macrophages. The contribution of MAFB to the homeostatic/anti-inflammatory macrophage profile is further supported by the skewed polarization of monocyte-derived macrophages from multicentric carpotarsal osteolysis (Online Mendelian Inheritance in Man #166300), a pathology caused by mutations in theMAFBgene. Our results demonstrate that MAFB critically determines the acquisition of the anti-inflammatory transcriptional and functional profiles of human macrophages.
authors.affiliation: Laboratorio de Células Mieloides, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain.
authors.forename: Víctor D
authors.identifier: 0000-0002-2816-8070
authors.initials: VD
authors.lastname: Cuevas
authors.affiliation: Servicio de Cirugía Ortopédica y Traumatología, Complejo Hospitalario de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
authors.forename: Laura
authors.identifier: 0000-0002-4196-5218
authors.initials: L
authors.lastname: Anta
authors.affiliation: Laboratorio de Inmuno-Oncología, Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain.
authors.forename: Rafael
authors.identifier: 0000-0002-3081-7332
authors.initials: R
authors.lastname: Samaniego
authors.affiliation: Laboratorio de Células Mieloides, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Orta-Zavalza
authors.affiliation: Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Científicas, 28029 Madrid, Spain.
authors.forename: Juan
authors.identifier: 0000-0003-1443-7548
authors.initials: J
authors.lastname: Vladimir de la Rosa
authors.affiliation: Unidad de Biomedicina, Instituto de Investigaciones Biomédicas-Universidad de Las Palmas de Gran Canaria (ULPGC), Instituto Universitario de Investigaciones Biomedicas y Sanitarias de la ULPGC, 35001 Las Palmas, Spain.|Département de Génétique, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, 75015 Paris, France; and.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Baujat
authors.affiliation: Laboratorio de Células Mieloides, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain.
authors.forename: Ángeles
authors.initials: Á
authors.lastname: Domínguez-Soto
authors.affiliation: Laboratorio de Inmuno-Oncología, Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Sánchez-Mateos
authors.affiliation: Institute for Applied Molecular Medicine, School of Medicine, University CEU San Pablo, Madrid, Spain.
authors.forename: María M
authors.initials: MM
authors.lastname: Escribese
authors.affiliation: Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Científicas, 28029 Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Castrillo
authors.affiliation: Unidad de Biomedicina, Instituto de Investigaciones Biomédicas-Universidad de Las Palmas de Gran Canaria (ULPGC), Instituto Universitario de Investigaciones Biomedicas y Sanitarias de la ULPGC, 35001 Las Palmas, Spain.|Département de Génétique, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, 75015 Paris, France; and.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.affiliation: Laboratorio de Células Mieloides, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain; acorbi@cib.csic.es mavega@cib.csic.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Vega
authors.affiliation: Laboratorio de Células Mieloides, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain; acorbi@cib.csic.es mavega@cib.csic.es.
authors.forename: Ángel L
authors.identifier: 0000-0003-1980-5733
authors.initials: ÁL
authors.lastname: Corbí
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016207:Cytokines / Q000378:metabolism; D055785:Gene Knockdown Techniques; D063990:Gene Ontology; D031845:Hajdu-Cheney Syndrome / Q000235:genetics / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D051258:MafB Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D059467:Transcriptome; D000098902:CD163 Antigen
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D011956:Receptors, Cell Surface; D016173:Macrophage Colony-Stimulating Factor