幼稚CD4 T细胞中与年龄相关的DNA甲基化变化表明衰老T细胞中自身免疫表观基因型在不断演变。
Age-associated DNA methylation changes in naive CD4 T cells suggest an evolving autoimmune epigenotype in aging T cells.
作者信息
Dozmorov Mikhail G, Coit Patrick, Maksimowicz-McKinnon Kathleen, Sawalha Amr H
机构信息
Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Epigenomics. 2017 Apr;9(4):429-445. doi: 10.2217/epi-2016-0143. Epub 2017 Mar 21.
AIM
We sought to define age-associated DNA methylation changes in naive CD4 T cells.
MATERIALS & METHODS: Naive CD4 T cells were collected from 74 healthy individuals (age 19-66 years), and age-related DNA methylation changes were characterized.
RESULTS
We identified 11,431 age-associated CpG sites, 57% of which were hypermethylated with age. Hypermethylated sites were enriched in CpG islands and repressive transcription factor binding sites, while hypomethylated sites showed T cell specific enrichment in active enhancers marked by H3K27ac and H3K4me1. Our data emphasize cancer-related DNA methylation changes with age, and also reveal age-associated hypomethylation in immune-related pathways, such as T cell receptor signaling, FCγR-mediated phagocytosis, apoptosis and the mammalian target of rapamycin signaling pathway. The MAPK signaling pathway was hypermethylated with age, consistent with a defective MAPK signaling in aging T cells.
CONCLUSION
Age-associated DNA methylation changes may alter regulatory mechanisms and signaling pathways that predispose to autoimmunity.
目的
我们试图确定初始CD4 T细胞中与年龄相关的DNA甲基化变化。
材料与方法
从74名健康个体（年龄19 - 66岁）中收集初始CD4 T细胞，并对与年龄相关的DNA甲基化变化进行表征。
结果
我们鉴定出11,431个与年龄相关的CpG位点，其中57%随年龄增长发生高甲基化。高甲基化位点在CpG岛和抑制性转录因子结合位点中富集，而低甲基化位点在以H3K27ac和H3K4me1标记的活性增强子中表现出T细胞特异性富集。我们的数据强调了与癌症相关的DNA甲基化随年龄的变化，同时也揭示了免疫相关途径中与年龄相关的低甲基化，如T细胞受体信号传导、FcγR介导的吞噬作用、凋亡和雷帕霉素哺乳动物靶标信号通路。丝裂原活化蛋白激酶（MAPK）信号通路随年龄增长发生高甲基化，这与衰老T细胞中MAPK信号缺陷一致。
结论
与年龄相关的DNA甲基化变化可能会改变易患自身免疫性疾病的调节机制和信号通路。
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