The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, in the presence and absence of calcitriol. Few DNA methylation changes occurred in cells treated with calcitriol. However, several VDR-binding sites demonstrated increased DNA methylation in cells of adult origin when compared to cells of paediatric origin. This phenomenon was not observed at other transcription factor binding sites. Genes associated with these sites were enriched for intracellular signalling and cell activation pathways involved in myeloid cell differentiation and adaptive immune system regulation. These results suggest vitamin D exposure at critical periods during development may contribute to latitude-related differences in autoimmune disease incidence.

中文翻译：

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年龄依赖性 VDR 峰值 DNA 甲基化作为纬度依赖性多发性硬化风险的机制

将紫外线辐射和维生素 D 暴露与获得纬度和关键时期依赖性自身免疫性疾病多发性硬化症风险联系起来的机制尚不清楚。我们检查了维生素 D 对成人和儿童骨髓细胞中维生素 D 受体结合位点 DNA 甲基化和 DNA 甲基化的影响。这是通过在存在和不存在骨化三醇的情况下将 CD34+ 造血祖细胞分化为 CD14+ 单核吞噬细胞来实现的。在用骨化三醇处理的细胞中几乎没有发生 DNA 甲基化变化。然而，与儿科细胞相比，几个 VDR 结合位点显示成人细胞中 DNA 甲基化增加。在其他转录因子结合位点没有观察到这种现象。与这些位点相关的基因富集了参与骨髓细胞分化和适应性免疫系统调节的细胞内信号传导和细胞激活途径。这些结果表明，在发育的关键时期接触维生素 D 可能会导致自身免疫性疾病发病率与纬度相关的差异。