Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients

Abstract

BackgroundMultiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. In this study we aim to identify DNA methylation changes associated with MS in CD8+ T cells in 30 relapsing remitting MS patients and 28 healthy blood donors using Illumina 450K methylation arrays.FindingsSeventy-nine differentially methylated CpGs were associated with MS. The methylation profile of CD8+ T cells was distinctive from our previously published data on CD4+ T cells in the same cohort. Most notably, there was no major CpG effect at the MS risk gene HLA-DRB1 locus in the CD8+ T cells.ConclusionCD8+ T cells and CD4+ T cells have distinct DNA methylation profiles. This case–control study highlights the importance of distinctive cell subtypes when investigating epigenetic changes in MS and other complex diseases.

Stochastics of Cellular Differentiation Explained by Epigenetics: The Case of T‐Cell Differentiation and Functional Plasticity

“…Moreover, genomewide DNA methylation studies have identified DMRs of CD4 T cells in MS patients compared to healthy controls, specifically on chromosome 6p21 at HLA‐DRB1 (a known MS risk locus), and additional non‐HLA CpGs that localized to genes linked with MS . Interestingly, the methylation profile of CD8 T cells in the same cohort of patients with relapsing remitting MS differed from CD4 T cells, supporting the notion that it is important to consider cell type‐specific epigenetic regulation . Mouse models of MS illustrate how targeting epigenetic mechanisms can also contribute to the design of novel therapies.…”

“…Scandinavian Journal of Immunology, 2017, 86,[184][185][186][187][188][189][190][191][192][193][194][195] 190 Epigenetics of T-Cell Differentiation genes linked with MS [77]. Interestingly, the methylation profile of CD8 T cells in the same cohort of patients with relapsing remitting MS differed from CD4 T cells, supporting the notion that it is important to consider cell type-specific epigenetic regulation [78]. Mouse models of MS illustrate how targeting epigenetic mechanisms can also contribute to the design of novel therapies.…”

CD8+T-cell transcription and DNA methylation show age specific differences and lack correlation with clinical outcome in pediatric Inflammatory Bowel Disease

“…DNA methylation has been shown to regulate key aspects of CD8 + T-cell function, including cellular differentiation and exhaustion 7 . Moreover, epigenetically mediated alterations in T-cell function have been implicated in disease pathogenesis of several immune mediated conditions 6,25,26 . We performed genome-wide DNA methylation profiling of CD8 + T-cells derived from children newly diagnosed with CD (n=66).…”

Vitamin D receptor gene is epigenetically altered and transcriptionally up-regulated in multiple sclerosis

“…PAD-2 destabilizes the myelin basic protein (MBP), which becomes an antigen for T cells [11]. Most recently, genome-wide DNA methylation profiling of CD8+ T and CD4+ T cells has shown distinct DNA methylation profiles in relapsing-remitting (RRMS) compared to healthy controls [12]. Importantly, methylation patterns of cell-free plasma DNA has been proposed as potential biomarkers for MS [13].…”