来源于单核细胞的巨噬细胞对炎症性疾病的发病起着贡献，它们的功效功能在很大程度上取决于优势的细胞外环境。M-CSF使巨噬细胞获取抗炎特征，而GM-CSF会驱动T细胞的刺激和促炎作用的巨噬细胞的生成。肝X受体（LXRα和LXRβ）是核受体，它们控制胆固醇代谢并调节组织驻留巨噬细胞的分化。类风湿关节炎和其他炎症病理学的巨噬细胞表现出富含的LXR途径，最近的报告表明LXR激活可以提高促炎效应并且有损M-CSF依赖的单核细胞来源的巨噬细胞（M-MØ）的获取抗炎特征。我们现在报道了LXR的抑制促进了在病理环境（类风湿关节炎患者的滑液）中以及人类单核细胞来源的巨噬细胞（GM-MØ）GM-CSF依赖分化时获取抗炎基因和功能特征的取得。机制上，LXR的抑制导致表达v-Maf鸟肌肉腱肌肉纤维肉瘤癌基因同源B（MAFB）转录因子更高的巨噬细胞，该转录因子统治着巨噬细胞的抗炎特征，以及MAFB调节的基因的过度表达。实际上，对人类巨噬细胞进行基因沉默实验表明MAFB对LXR抑制剂增强人类巨噬细胞的抗炎性是必需的。总之，我们的结果表明LXR抑制可以以MAFB依赖的方式促进人类巨噬细胞获取抗炎转录和功能特征，并提出使用LXR拮抗剂作为炎症反应期间巨噬细胞再编程策略的潜在治疗替代方案。© 2023.作者。

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.© 2023. The Author(s).