Demethylation of Promoter Regulatory Elements Contributes to Perforin Overexpression in CD4+ Lupus T Cells

摘要: Inhibiting DNA methylation in CD4+ T cells causes aberrant gene expression and autoreactive monocyte/macrophage killing vitro, the hypomethylated cause a lupus-like disease animal models. Similar decreases cell occur idiopathic lupus, potentially contributing to pathogenesis. The genes affected by hypomethylation are largely unknown. Using inhibitors oligonucleotide arrays we have identified perforin as methylation-sensitive gene. Our group has also reported that increase demethylating conserved region is primary CD8+ cells, which express perforin, but methylated do not. As lupus promiscuously kill autologous monocytes/macrophages, hypothesized may be similarly overexpressed contribute monocyte killing. We report from patients with active, not inactive, overexpress overexpression related demethylation of same sequences suppressing transcription demethylated inhibitors. Further, inhibitor concanamycin A blocks suggesting functional. conclude specific regulatory elements contributes cells. results suggest