Characterization of Altered Gene Expression and Histone Methylation in Peripheral Blood Mononuclear Cells Regulating Inflammation in COVID-19 Patients.

Abstract

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.

• Authors: Xiaoming Yang, Alex C Rutkovsky, Juhua Zhou, Yin Zhong, Julian Reese, Timothy Schnell, Helmut Albrecht, William B Owens, Prakash S Nagarkatti, Mitzi Nagarkatti
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 208 Issue 8 Pg. 1968-1977 (04 15 2022) ISSN: 1550-6606 [Electronic] United States
• PMID: 35379747 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 by The American Association of Immunologists, Inc.

Chemical References

• Histones
• Receptors, Interleukin-1

Topics

• COVID-19 (genetics, metabolism)
• DNA Methylation
• Epigenesis, Genetic (physiology)
• Gene Expression
• Histones (metabolism)
• Humans
• Inflammation (genetics, metabolism)
• Leukocytes, Mononuclear (metabolism)
• Receptors, Interleukin-1 (metabolism)
• Transcriptome
• COVID-19 Drug Treatment