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首页> 美国卫生研究院文献>Oncotarget >Histone demethylase JMJD3 regulates CD11a expression through changes in histone H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus erythematosus
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Histone demethylase JMJD3 regulates CD11a expression through changes in histone H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus erythematosus

机译：组蛋白去甲基化酶JMJD3通过改变系统性红斑狼疮患者CD4 + T细胞中组蛋白H3K27三甲基化水平来调节CD11a表达

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Aberrant CD11a overexpression in CD4+ T cells induces T cell auto-reactivity, which is an important factor for systemic lupus erythematosus (SLE) pathogenesis. Although many studies have focused on CD11a epigenetic regulation, little is known about histone methylation. JMJD3, as a histone demethylase, is capable of specifically removing the trimethyl group from the H3K27 lysine residue, triggering target gene activation. Here, we examined the expression and function of JMJD3 in CD4+ T cells from SLE patients. Significantly decreased H3K27me3 levels and increased JMJD3 binding were detected within the ITGAL (CD11a) promoter locus in SLE CD4+ T cells compared with those in healthy CD4+ T cells. Moreover, overexpressing JMJD3 through the transfection of pcDNA3.1-JMJD3 into healthy donor CD4+ T cells increased JMJD3 enrichment and decreased H3K27me3 enrichment within the ITGAL (CD11a) promoter and up-regulated CD11a expression, leading to T and B cell hyperactivity. Inhibition of JMJD3 via JMJD3-siRNA in SLE CD4+ T cells showed the opposite effects. These results demonstrated that histone demethylase JMJD3 regulates CD11a expression in lupus T cells by affecting the H3K27me3 levels in the ITGAL (CD11a) promoter region, and JMJD3 might thereby serve as a potential therapeutic target for SLE.
机译：CD4 + T细胞中异常的CD11a过表达诱导T细胞自身反应，这是系统性红斑狼疮（SLE）发病机理的重要因素。尽管许多研究集中于CD11a表观遗传调控，但对组蛋白甲基化知之甚少。 JMJD3作为组蛋白脱甲基酶，能够从H3K27赖氨酸残基上特异性去除三甲基，从而触发靶基因激活。在这里，我们检查了JMJD3在SLE患者CD4 + T细胞中的表达和功能。与健康的CD4 + T细胞相比，SLE CD4 + T细胞中ITGAL（CD11a）启动子基因座中的H3K27me3水平显着降低，而JMJD3结合增加。此外，通过将pcDNA3.1-JMJD3转染到健康供体CD4 + T细胞中过表达JMJD3可以增加ITGAL（CD11a）启动子中JMJD3的富集并降低H3K27me3的富集，并上调CD11a的表达，从而导致T和B细胞过度活跃。 JMJD3-siRNA对SLE CD4 + T细胞抑制JMJD3表现出相反的作用。这些结果表明，组蛋白脱甲基酶JMJD3通过影响ITGAL（CD11a）启动子区域的H3K27me3水平来调节狼疮T细胞中的CD11a表达，因此JMJD3可能成为SLE的潜在治疗靶标。

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