DNA 甲基化调控模式及其在变应性鼻炎和慢性自发性荨麻疹共同发病机制中的潜在途径。
DNA methylation regulatory patterns and underlying pathways behind the co-pathogenesis of allergic rhinitis and chronic spontaneous urticaria.
机构信息
Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
出版信息
Front Immunol. 2023 Jan 11;13:1053558. doi: 10.3389/fimmu.2022.1053558. eCollection 2022.
BACKGROUND
Allergic rhinitis (AR) and chronic spontaneous urticaria (CSU) are often concurrent in patients. Changes in DNA methylation affect T cell biological processes, which may explain the occurrence and progression of comorbidity. However, downstream regulatory pathways of DNA methylation in two diseases and the underlying mechanisms have not been fully elucidated.
METHODS
The GSE50101, GSE72541, GSE50222 and OEP002482 were mined for the identification of differentially expressed genes (DEGs) or co-expressed genes and differentially methylated genes (DMGs) in AR and CSU patients. We applied GO analysis and consensus clustering to study the potential functions and signal pathways of selected genes in two diseases. GSVA and logistic regression analysis were used to find the regulatory pathway between DNA methylation and activation patterns of CD4+ T cells. Besides, we used the Illumina 850k chip to detect DNA methylation expression profiles and recognize the differentially methylated CpG positions (DMPs) on corresponding genes. Finally, we annotated the biological process of these genes using GO and KEGG pathway analysis.
RESULT
The AR-related DEGs were found closely related to the differentiation and activation of CD4+ T cells. The DEGs or co-expressed genes of CD4+ T cells in AR and CSU patients were also clustered using GO and KEGG analysis and we got 57 co-regulatory pathways. Furthermore, logistic regression analysis showed that the regulation of cellular component size was closely related to the activation of CD4+ T cells regulated by DNA methylation. We got self-tested data using the Illumina 850k chip and identified 98 CpGs that were differentially methylated in patients. Finally, we mapped the DMPs to 15 genes and found that they were mainly enriched in the same CD4+T cell regulating pathway.
CONCLUSION
Our study indicated that DNA methylation affected by pollen participated in the activation patterns of CD4 + T cells, providing a novel direction for the symptomatic treatment of the co-occurrence of AR and CSU.
背景
变应性鼻炎（AR）和慢性自发性荨麻疹（CSU）常同时发生在患者中。DNA 甲基化的改变影响 T 细胞的生物学过程，这可能解释了共病的发生和进展。然而，两种疾病中 DNA 甲基化的下游调控途径及其潜在机制尚未完全阐明。
方法
挖掘 GSE50101、GSE72541、GSE50222 和 OEP002482 数据集，以鉴定 AR 和 CSU 患者中差异表达基因（DEGs）或共表达基因和差异甲基化基因（DMGs）。我们应用 GO 分析和共识聚类来研究两种疾病中选定基因的潜在功能和信号通路。GSVA 和逻辑回归分析用于发现 DNA 甲基化与 CD4+T 细胞激活模式之间的调控途径。此外，我们使用 Illumina 850k 芯片检测 DNA 甲基化表达谱，并识别相应基因上差异甲基化的 CpG 位置（DMPs）。最后，我们使用 GO 和 KEGG 通路分析注释这些基因的生物学过程。
结果
AR 相关的 DEGs 与 CD4+T 细胞的分化和激活密切相关。AR 和 CSU 患者 CD4+T 细胞的 DEGs 或共表达基因也通过 GO 和 KEGG 分析聚类，我们得到了 57 个共调控途径。此外，逻辑回归分析表明，细胞成分大小的调节与 DNA 甲基化调控的 CD4+T 细胞激活密切相关。我们使用 Illumina 850k 芯片进行了自我测试，并鉴定出 98 个在患者中差异甲基化的 CpG。最后，我们将 DMPs 映射到 15 个基因上，发现它们主要富集在相同的 CD4+T 细胞调节途径中。
结论
我们的研究表明，花粉介导的 DNA 甲基化参与了 CD4+T 细胞的激活模式，为 AR 和 CSU 共病的对症治疗提供了新的方向。
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