首页> 外文期刊>Nature immunology >IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses.
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IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses.

机译:IRF5促进炎症性巨噬细胞极化和TH1-TH17反应。

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摘要

Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and repressed the gene encoding IL-10. Consequently, those macrophages set up the environment for a potent T helper type 1 (T(H)1)-T(H)17 response. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and define a previously unknown function for IRF5 as a transcriptional repressor.
机译:导致更高的mRNA表达的编码转录因子IRF5的基因多态性与许多自身免疫性疾病有关。在这里,我们显示IRF5在巨噬细胞中的表达是由炎症刺激可逆诱导的,并有助于巨噬细胞极化的可塑性。 IRF5的高表达是M1巨噬细胞的特征,它直接激活编码白介素12亚基p40(IL-12p40),IL-12p35和IL-23p19的基因的转录,并抑制编码IL-10的基因。因此,那些巨噬细胞为强效的1型T辅助细胞(T(H)1)-T(H)17应答建立了环境。全局基因表达分析表明,外源IRF5分别上调或下调了M1或M2巨噬细胞已建立表型标记的表达。我们的数据表明IRF5在M1巨噬细胞极化中的关键作用,并定义了IRF5作为转录阻遏物的以前未知的功能。

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