Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/121744
Título: Inhibition of LXR controls the polarization of human inflammatory macrophages through upregulation of MAFB
Autores/as: González de la Aleja, Arturo
Herrero, Cristina
Torres-Torresano, Mónica
Schiaffino, María Teresa
del Castillo, Alejandro
Alonso, Bárbara
Vega, Miguel A.
Puig-Kröger, Amaya
Castrillo Viguera, Antonio 
Corbí, Ángel L.
Clasificación UNESCO: 32 Ciencias médicas
320509 Reumatología
2407 Biología celular
Palabras clave: Inflammation
Innate Immunity
Macrophage Polarization
Transcriptional Profile
Fecha de publicación: 2023
Publicación seriada: Cellular and Molecular Life Sciences 
Resumen: Monocyte-derived macrophages contribute to pathogenesis in inflammatory diseases and their effector functions greatly depend on the prevailing extracellular milieu. Whereas M-CSF primes macrophages for acquisition of an anti-inflammatory profile, GM-CSF drives the generation of T cell-stimulatory and pro-inflammatory macrophages. Liver X Receptors (LXRα and LXRβ) are nuclear receptors that control cholesterol metabolism and regulate differentiation of tissue-resident macrophages. Macrophages from rheumatoid arthritis and other inflammatory pathologies exhibit an enriched LXR pathway, and recent reports have shown that LXR activation raises pro-inflammatory effects and impairs the acquisition of the anti-Inflammatory profile of M-CSF-dependent monocyte-derived macrophages (M-MØ). We now report that LXR inhibition prompts the acquisition of an anti-inflammatory gene and functional profile of macrophages generated within a pathological environment (synovial fluid from Rheumatoid Arthritis patients) as well as during the GM-CSF-dependent differentiation of human monocyte-derived macrophages (GM-MØ). Mechanistically, inhibition of LXR results in macrophages with higher expression of the v-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog B (MAFB) transcription factor, which governs the macrophage anti-inflammatory profile, as well as over-expression of MAFB-regulated genes. Indeed, gene silencing experiments on human macrophages evidenced that MAFB is required for the LXR inhibitor to enhance the anti-inflammatory nature of human macrophages. As a whole, our results demonstrate that LXR inhibition prompts the acquisition of an anti-inflammatory transcriptional and functional profile of human macrophages in a MAFB-dependent manner, and propose the use of LXR antagonists as potential therapeutic alternatives in macrophage re-programming strategies during inflammatory responses.
URI: http://hdl.handle.net/10553/121744
ISSN: 1420-682X
DOI: 10.1007/s00018-023-04745-4
Fuente: Cellular and Molecular Life Sciences [ISSN 1420-682X], v. 80 (4): 96, (Abril 2023)
Colección:Artículos
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