Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC; and.
Prisma Health Richland Hospital, School of Medicine, University of South Carolina, Columbia, SC.
J Immunol. 2022 Apr 15;208(8):1968-1977. doi: 10.4049/jimmunol.2101099. Epub 2022 Apr 4.
The pandemic of COVID-19 has caused >5 million deaths in the world. One of the leading causes of the severe form of COVID-19 is the production of massive amounts of proinflammatory cytokines. Epigenetic mechanisms, such as histone/DNA methylation, miRNA, and long noncoding RNA, are known to play important roles in the regulation of inflammation. In this study, we investigated if hospitalized COVID-19 patients exhibit alterations in epigenetic pathways in their PBMCs. We also compared gene expression profiles between healthy controls and COVID-19 patients. Despite individual variations, the expressions of many inflammation-related genes, such as arginase 1 and IL-1 receptor 2, were significantly upregulated in COVID-19 patients. We also found the expressions of coagulation-related genes Von Willebrand factor and protein S were altered in COVID-19 patients. The expression patterns of some genes, such as IL-1 receptor 2, correlated with their histone methylation marks. Pathway analysis indicated that most of those dysregulated genes were in the TGF-β, IL-1b, IL-6, and IL-17 pathways. A targeting pathway revealed that the majority of those altered genes were targets of dexamethasone, which is an approved drug for COVID-19 treatment. We also found that the expression of bone marrow kinase on chromosome X, a member of TEC family kinases, was increased in the PBMCs of COVID-19 patients. Interestingly, some inhibitors of TEC family kinases have been used to treat COVID-19. Overall, this study provides important information toward identifying potential biomarkers and therapeutic targets for COVID-19 disease.
COVID-19 大流行已在全球造成超过 500 万人死亡。COVID-19 严重形式的主要原因之一是大量促炎细胞因子的产生。表观遗传机制，如组蛋白/DNA 甲基化、miRNA 和长非编码 RNA，已知在炎症调节中发挥重要作用。在这项研究中，我们研究了住院 COVID-19 患者的 PBMCs 中是否存在表观遗传途径的改变。我们还比较了健康对照和 COVID-19 患者之间的基因表达谱。尽管存在个体差异，但 COVID-19 患者中许多炎症相关基因的表达，如精氨酸酶 1 和 IL-1 受体 2，显著上调。我们还发现 COVID-19 患者中凝血相关基因血管性血友病因子和蛋白 S 的表达发生改变。一些基因的表达模式，如 IL-1 受体 2，与其组蛋白甲基化标记相关。通路分析表明，大多数失调基因位于 TGF-β、IL-1b、IL-6 和 IL-17 通路中。靶向通路分析表明，大多数改变的基因是地塞米松的靶点，地塞米松是一种批准用于 COVID-19 治疗的药物。我们还发现，X 染色体上骨髓激酶的表达，TEC 家族激酶的一个成员，在 COVID-19 患者的 PBMCs 中增加。有趣的是，一些 TEC 家族激酶抑制剂已被用于治疗 COVID-19。总体而言，这项研究为确定 COVID-19 疾病的潜在生物标志物和治疗靶点提供了重要信息。
