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MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis

Authors
  • Cuevas, Víctor D.
  • Anta, Laura
  • Samaniego, Rafael
  • Orta-Zavalza, Emmanuel
  • Vladimir de la Rosa, Juan
  • Baujat, Geneviève
  • Domínguez-Soto, Ángeles
  • Sánchez-Mateos, Paloma
  • Escribese, María M.
  • Castrillo, Antonio
  • Valérie Cormier-Daire
  • Vega, Miguel A.
  • Corbí, Ángel L.
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Jul 13, 2017
Volume
198
Issue
5
Pages
2070–2081
Identifiers
DOI: 10.4049/jimmunol.1601667
PMID: 28093525
Source
USPC - SET - SVS
License
Green

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 the MAFB gene. Our results demonstrate that MAFB critically determines the acquisition of the anti-inflammatory transcriptional and functional profiles of human macrophages.

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