PDF(Pubmed)
Abstract：
Monocyte-derived macrophages, the major source of pathogenic macrophages in COVID-19, are oppositely instructed by macrophage CSF (M-CSF) or granulocyte macrophage CSF (GM-CSF), which promote the generation of antiinflammatory/immunosuppressive MAFB+ (M-MØ) or proinflammatory macrophages (GM-MØ), respectively. The transcriptional profile of prevailing macrophage subsets in severe COVID-19 led us to hypothesize that MAFB shapes the transcriptome of pulmonary macrophages driving severe COVID-19 pathogenesis. We have now assessed the role of MAFB in the response of monocyte-derived macrophages to SARS-CoV-2 through genetic and pharmacological approaches, and we demonstrate that MAFB regulated the expression of the genes that define pulmonary pathogenic macrophages in severe COVID-19. Indeed, SARS-CoV-2 potentiated the expression of MAFB and MAFB-regulated genes in M-MØ and GM-MØ, where MAFB upregulated the expression of profibrotic and neutrophil-attracting factors. Thus, MAFB determines the transcriptome and functions of the monocyte-derived macrophage subsets that underlie pulmonary pathogenesis in severe COVID-19 and controls the expression of potentially useful biomarkers for COVID-19 severity.
摘要：
单核细胞来源的巨噬细胞,COVID-19中致病性巨噬细胞的主要来源，与M-CSF或GM-CSF相反，促进抗炎/免疫抑制MAFB+（M-MØ）或促炎巨噬细胞（GM-MØ）的产生，分别。严重COVID-19中普遍存在的巨噬细胞亚群的转录谱使我们假设MAFB塑造了驱动严重COVID-19发病机制的肺巨噬细胞转录组。我们现在已经通过遗传和药理学方法评估了MAFB在单核细胞衍生的巨噬细胞对SARS-CoV-2的反应中的作用。并证明MAFB调节重症COVID-19中定义肺致病性巨噬细胞的基因的表达。的确,SARS-CoV-2增强了M-MØ和GM-MØ中MAFB和MAFB调节基因的表达，其中MAFB上调促纤维化因子和嗜中性粒细胞吸引因子的表达。因此，MAFB确定单核细胞衍生的巨噬细胞亚群的转录组和功能，这些亚群是严重COVID-19肺部发病机理的基础，并控制COVID-19严重程度的潜在有用生物标志物的表达。
