GSE183257
Epigenetic and Transcriptional Dysregulation in T cells of patients with Atopic Dermatitis [ATAC-seq]
Atopic dermatitis (AD), the start of the atopic march, is one of the most common skin disorders in children. Immunologically, AD involves skin barrier defects and CD4+ T cells that localize to the skin, producing inflammatory cytokines and amplifying epidermal dysfunction. To understand the gene regulatory activity differences in peripheral blood T cells in AD, we measured chromatin accessibility (ATAC-seq), NFKB1 binding (ChIP-seq), and gene expression (RNA-seq) in stimulated CD4+ T cells from subjects with active moderate-to-severe AD and age-matched healthy, non-allergic controls. Chromatin accessibility in stimulated CD4+ T cells were highly enriched for AD genetic risk variants. The vast majority of ATAC-seq peaks were shared, consistent with those sections of chromatin being equally available between matched pairs; however, NFKB DNA binding motifs were enriched in chromatin accessible in an AD-dependent manner. NFKB1 ChIP-seq identified peaks that were stronger in AD cases, enriched in controls, or shared between cases and controls. The ChIP-seq peaks that were statistically stronger in AD were more strongly enriched for NFKB DNA binding motifs. Chromatin that was more strongly accessibe and bound by NFKB1 in AD were enriched for genetic variants that increase risk for AD. Using whole genome sequencing data, we identified wide-spread genotype-dependent chromatin accessibility and allelic NFKB1 binding at AD and allergic disease genetic risk loci. Overall design: ATAC-seq was performed in stimulated CD4+ T cells from 6 subjects with active moderate-to-severe AD and 6 age-matched healthy, non-allergic controls.