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Título: | Activation of LXR nuclear receptors impairs the anti-inflammatory gene and functional profile of M-CSF-dependent human monocyte-derived macrophages |
Autor: | González de la Aleja, Arturo CSIC ORCID ; Herrero, Cristina CSIC; Torres-Torresano, Mónica; Rosa, Juan Vladimir de la; Alonso, Bárbara CSIC; Capa-Sardón, Enrique; Muller, Ittai B.; Jansen, Gerrit; Puig-Kröger, Amaya CSIC ORCID; Vega Palacios, Miguel A. ; Castrillo, Antonio CSIC ORCID; Corbí, Angel L. | Palabras clave: | Innate immunity Macrophage Macrophage polarization LXR Inflammation |
Fecha de publicación: | 24-feb-2022 | Editor: | Frontiers Media | Citación: | Frontiers in Immunology 13: 835478 (2022) | Resumen: | Liver X Receptors (LXR) control cholesterol metabolism and exert anti-inflammatory actions but their contribution to human macrophage polarization remains unclear. The LXR pathway is enriched in pro-inflammatory macrophages from rheumatoid arthritis as well as in tumors-associated macrophages from human tumors. We now report that LXR activation inhibits the anti-inflammatory gene and functional profile of M-CSF-dependent human macrophages, and prompts the acquisition of a pro-inflammatory gene signature, with both effects being blocked by an LXR inverse agonist. Mechanistically, the LXR-stimulated macrophage polarization shift correlates with diminished expression of MAFB and MAF, which govern the macrophage anti-inflammatory profile, and with enhanced release of activin A. Indeed, LXR activation impaired macrophage polarization in response to tumor-derived ascitic fluids, as well as the expression of MAF- and MAFB-dependent genes. Our results demonstrate that LXR activation limits the anti-inflammatory human macrophage polarization and prompts the acquisition of an inflammatory transcriptional and functional profile. | Descripción: | 13 p.-7 fig. | Versión del editor: | https://doi.org/10.3389/fimmu.2022.835478 | URI: | http://hdl.handle.net/10261/262185 | DOI: | 10.3389/fimmu.2022.835478 | E-ISSN: | 1664-3224 |
Aparece en las colecciones: | (CIB) Artículos (IIBM) Artículos |
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Frontiers in Immunology_González de Aleja_2022.pdf | Artículo principal | 9,27 MB | Adobe PDF | Visualizar/Abrir |
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