Sex-based comparison of CD4+ T cell DNA methylation in lupus reveals proinflammatory epigenetic changes in men.
Sex-based comparison of CD4+ T cell DNA methylation in lupus reveals proinflammatory epigenetic changes in men.
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DOI：
10.1016/j.clim.2022.109116
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发表时间：
2022-10
期刊：
影响因子：
--
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中科院分区：
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--
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系统性红斑狼疮(SLE)在女性中比男性更常见，但当它影响男性时，这种疾病更严重。狼疮患者的CD4+T细胞表现出异常的DNA甲基化模式。这项研究的目的是研究SLE患者男性(n=12)和女性(n=10)的全基因组CD4+T细胞差异DNA甲基化。用Infinium甲基化EPIC阵列评估DNA甲基化，并通过调整年龄和疾病活动性的探针式线性回归计算男性和女性SLE患者之间的差异。我们在男性和女性SLE患者的CD4+T细胞中发现了198个低甲基化和108个高甲基化的CpG位点，分别注释为201和102个基因。其中很大一部分基因与细胞凋亡和免疫功能有关。在差异甲基化基因中，参与外源性细胞凋亡途径的CASP10和多个参与T细胞功能和分化的基因如ELAVL1、uhrf1和Smad2在男性SLE患者中存在低甲基化。重要的是，对差异甲基化基因的网络分析显示，与女性相比，男性SLE患者ROCK、PP2A、PI3K和ERK1/ERK2的激活增加是一致的。这些数据提供了表观遗传学证据，表明与女性相比，男性SLE患者的关键T细胞通路被激活，并为男性SLE疾病严重性增加的可能机制提供了新的线索。
Systemic lupus erythematosus (SLE) is more common in women than men, but the disease is more severe when it affects men. Lupus CD4+ T cells demonstrate dysregulated DNA methylation patterns. The purpose of this study was to investigate genome-wide CD4+ T cell differential DNA methylation between men (n = 12) and women (n = 10) with SLE. DNA methylation was evaluated using the Infinium MethylationEPIC array, and differences between male versus female SLE patients were calculated with probe-wise linear regressions with adjustment for age and disease activity. We identified 198 hypomethylated and 108 hypermethylated CpG sites in CD4+ T cells isolated from male compared to female SLE patients, annotated to 201 and 102 genes, respectively. A great proportion of these genes were related to apoptosis and immune functions. Among differentially methylated genes, CASP10, which is involved in the extrinsic apoptotic pathway, and multiple genes involved in T cell function and differentiation such as ELAVL1, UHRF1, and SMAD2, were hypomethylated in men compared to women with SLE. Importantly, network analysis of differentially methylated genes revealed a pattern consistent with increased activation of ROCK, PP2A, PI3K, and ERK1/ERK2 in men compared to women with SLE. These data provide epigenetic evidence suggesting activation of key T cell pathways in men compared to women with SLE and shed new light into possible mechanisms underlying increased SLE disease severity in men.
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DOI：
10.4049/jimmunol.2001266
发表时间：
2021-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Pan W;Nagpal K;Suárez-Fueyo A;Ferretti A;Yoshida N;Tsokos MG;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
DOI：
10.1016/j.clim.2016.04.010
发表时间：
2017-12
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Koga T;Ichinose K;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
系统性红斑狼疮
影响因子：
81.5
作者：
Kaul, Arvind;Gordon, Caroline;Hughes, Graham
通讯作者：
Hughes, Graham