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Transcriptome Analysis and Emerging Driver Identification of CD8+ T Cells in Patients with Vitiligo

机译:白癜风患者CD8 + T细胞的转录组分析及新兴探测鉴定

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Activated CD8+ T cells play important roles in the pathogenesis of vitiligo. However, driving factors about the activation and migration of CD8+ T cells remain obscure. In this study, we aim to identify differentially expressed genes (DEGs) and uncover potential factors that drive the disease in melanocyte-specific CD8+ T cells in vitiligo. A total of 1147 DEGs were found through transcriptome sequencing in CD8+ T cells from lesional skin of vitiligo patients and normal controls. Based on KEGG pathway enrichment analysis and PPI, 16 upregulated and 23 downregulated genes were identified. Ultimately, 3 genes were figured out after RT-qPCR verification. The mRNA and protein expression levels of PIK3CB, HIF-1α, and F2RL1 were all elevated in CD8+ T cells from peripheral blood in vitiligo. HIF-1α and PIK3CB were significantly increased in lesional skin of vitiligo. Two CpG sites of the HIF-1α promoter were hypomethylated in vitiligo CD8+ T cells. In conclusion, HIF-1α, F2RL1, and PIK3CB may act as novel drivers for vitiligo, which are all closely associated with reactive oxygen species and possibly contribute to the activation and/or migration of melanocyte-specific CD8+ T cells in vitiligo. In addition, we uncovered a potential role for DNA hypomethylation of HIF-1α in CD8+ T cells of vitiligo.
机译:活化的CD8 + T细胞在白癜风的发病机制中起重要作用。然而,关于CD8 + T细胞的激活和迁移的驱动因素仍然模糊不清。在这项研究中,我们的目的是鉴定差异表达的基因(DEGS),并在白癜风中揭示在黑素细胞特异性CD8 + T细胞中驱动该疾病的潜在因素。通过来自白癜风患者的损伤皮肤和正常对照的CD8 + T细胞中的转录组测序,共有1147次。基于KEGG途径富集分析和PPI,鉴定了16个上调和23个下调基因。最终,在RT-QPCR验证后发现了3个基因。 PIK3CB,HIF-1α和F2RL1的mRNA和蛋白表达水平全部在Vitiligo的外周血中升高到CD8 + T细胞中。在白癜风的损害皮肤中,HIF-1α和PIK3CB显着增加。 HIF-1α启动子的两个CPG位点在白癜风CD8 + T细胞中甲基化。总之,HIF-1α,F2RL1和PIK3CB可以充当白癜风的新型司机,其与反应性氧物质密切相关,并且可能有助于在白癜风中的黑素细胞特异性CD8 + T细胞的活化和/或迁移。此外,我们发现在白癜风的CD8 + T细胞中HIF-1α的DNA低甲基化的潜在作用。

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