期刊
CLINICAL EPIGENETICS
卷 14, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13148-022-01399-0
关键词
Immune response; Immune activation; CD4 T cell; CD8 T cell; B cell; TEMRA; Central memory cell; Effector memory cell; DNA methylation
资金
- 2018 AACR-Johnson & Johnson Lung Cancer Innovation Science [R01CA216265]
- CDMRP/Department of Defense [R01CA253976]
- NIGMS [W81XWH-20-1-0778]
- Magnin Newman Endowment for Neurooncology [P30 CA168524, P20 GM130423, P20GM103428, R01 CA207360, P50 CA097257]
- [18-90-52-MICH]
- [P20GM104416/8299]
This study reveals shared epigenetic regulation during memory cell differentiation in immune cell lineages. Distinct DNA methylation changes were observed in different cell lineages during central to effector memory differentiation. Additionally, unique DNA methylation patterns were found in terminally differentiated effector memory cells.
Background: There is considerable evidence that epigenetic mechanisms and DNA methylation are critical drivers of immune cell lineage differentiation and activation. However, there has been limited coordinated investigation of common epigenetic pathways among cell lineages. Further, it remains unclear if long-lived memory cell subtypes differentiate distinctly by cell lineages. Results: We used the Illumina EPIC array to investigate the consistency of DNA methylation in B cell, CD4 T, and CD8 T naive and memory cells states. In the process of naive to memory activation across the three lineages, we identify considerable shared epigenetic regulation at the DNA level for immune memory generation. Further, in central to effector memory differentiation, our analyses revealed specific CpG dinucleotides and genes in CD4 T and CD8 T cells with DNA methylation changes. Finally, we identified unique DNA methylation patterns in terminally differentiated effector memory (TEMRA) CD8 T cells compared to other CD8 T memory cell subtypes. Conclusions: Our data suggest that epigenetic alterations are widespread and essential in generating human lymphocyte memory. Unique profiles are involved in methylation changes that accompany memory genesis in the three subtypes of lymphocytes.
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