Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells [Affymetrix]

Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells reveals long range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci range dysregulation of key inflammatory pathways mediated by disease-associated System sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis. In this study, we obtained DNA methylation and RNA expression profiles of CD4+ T cells from 48 SSc patients and 16 healthy controls. Consequently, we identified 9112 and 3929 differentially methylated CpGs positions (DMPs) and differentially expressed genes (DEGs) respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing promoter capture Hi-C data, we confirmed 168 pairs of DMP-DEG physical interactions. Finally, utilizing SSc GWAS data, we identified three important SSc-associated susceptibility loci, CSK (rs1378942), IL12RB1 (rs2305743) and IKZF3-GSDMB (rs9303277), that physically interact with cg11062629-ULK3, cg10808810-JUND and cg19458020-CCR7 respectively. Overall, our study reveals a solid link between genetic, epigenetic and transcriptional deregulation in CD4+ T cells of SSc patients, providing further understanding to SSc pathogenesis. CD4+ T cells were isolated from peripheral blood of 48 SSc patients and 16 healthy donors by positive cell sorting.