Oral tolerance induction in experimental autoimmune encephalomyelitis with Candida expressing a specific Mog peptide

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with altered immune responses in autoimmune diseases. Since in the mixed populations of peripheral blood mononuclear cells (PBMCs) cell-specific methylation is masked, determination of methylation profiles of distinct immune cell subsets is of most importance for studies of immune-mediated disease states. In this study, our goal was to characterize the relationship of expression and methylation profiles in four human immune cell subsets: B cells, monocytes, CD4 and CD8 T cells obtained from healthy donors. The cell subsets were purified from five healthy females by FACs sorting; RNA and DNA were extracted and hybridized to HumanHT-12 and HumanMethylation450 bead chips respectively. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) between the four subsets were identified, and distinct methylation and expression profiles characterized. Classification of the DMRs based on their genomic position relatively to the transcription start site or CpG islands identified a strong enrichment of DMRs in genebodies and CpG shores. Combining our data of females with similar data of males from the public domain highlighted gender specific methylation in about 10% of the CpG sites shared by all cell subsets. However, the cell specific DMRs we identified in the male dataset highly overlap with the cell-specific DMRs identified in females, with hardly any gender effect. The correlation between methylation and expression profile was assessed in both datasets in each of the four subsets, revealing both positive and negative correlations, the latter being the most frequent in all subsets. Pathway analysis of the CD14 subset data showed that negatively correlated genes were enriched in a pathway of inflammatory response, while positively correlated genes were enriched in cell death. Our results provide data to study the complex relationships between methylation and gene expression. Furthermore, the obtained expression and methylation profiles may serve as control references for studies of immune-cell profiles in patients with autoimmune diseases.