Comparative analysis of the DNA methylation landscape in CD4, CD8, and B memory lineages

Abstract

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 naïve and memory cells states. In the process of naïve 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.

Exploring Memory Function Beyond Immune Cells: ANGPTL4‐Mediated Memory Functions in Tissue Resident Stem Cells

“…It has recently attracted considerable attention. [ 26 ] Recent studies have highlighted the involvement of histone H3 modifications in the regulation of memory function in various immune cells, particularly T cells and B cells. [ 27 ] Particularly, various methylation forms of histone H3 at lysine 4 (namely H3K4me1, H3K4me2, and H3K4me3) and lysine 9 (namely H3K9me1, H3K9me2, and H3K9me3) play distinct roles in regulating immune memory responses.…”

Calculating Detection Limits and Uncertainty of Reference-Based Deconvolution of Whole-Blood DNA Methylation Data

“…Both naive CD4 and CD8 T cells are derived from a common lymphoid progenitor and undergo peripheral priming with antigen and the subsequent generation of memory and effector populations [ 43 ]. Thus, CD4 and CD8 T naive and memory cells are closely related in cell lineage and, furthermore, our studies have shown that each cell type shares epigenetic programs that are involved in the naive-to-memory cell transition [ 44 ]. Thus, uncertainty is expected to be greatest in discriminating closely related cells that share chromatin modifications in their terminal differentiation.…”

Impact of Plasmodium falciparum infection on DNA methylation of circulating immune cells

“…Epigenetic studies have begun to establish mechanistic links between epigenetic regulation and diseases susceptibility such as for rheumatoid arthritis ( Liu et al, 2013 ) and type I diabetes ( Rakyan et al, 2011 ) and also variation in immune-related gene expression traits ( Lim et al, 2013 ; Obata et al, 2015 ), immune cell differentiation processes ( Lai et al, 2013 ; Netea et al, 2015 ; Sellars et al, 2015 ; Rusek et al, 2018 ; Sun and Barreiro, 2020 ), immune memory genesis. For instance, Zhang and colleagues investigated the role of epigenetic mechanisms and DNA methylation in immune cell lineage differentiation and memory generation and reported specific DNA methylation patterns involved in the differentiation of memory cell subtypes with shared epigenetic regulation mechanisms across different immune cell lineages ( Zhang et al, 2022 ). Despite the growing appreciation of the role of host epigenetics in the host immune response to pathogens such as Mycobacterium tuberculosis ( Pennini et al, 2006 ; Gómez-Díaz et al, 2012 ; Cheeseman and Weitzman, 2015 ; Pacis et al, 2015 ), Leishmania donovani ( Marr et al, 2014 ), and Toxoplasma gondii ( Sabou et al, 2020 ), knowledge on the role of host epigenetic modifications in malaria is limited.…”