Lupus flares when genetically predisposed people encounter certain environmental agents. How the environment alters the immune response to cause flares is unclear. The treatment of lupus is also imperfect, often requiring drugs with significant toxicities. Understanding how the environment causes lupus flares could indicate safer and more effective treatments. The lupus-inducing drugs procainamide and hydralazine, as well as oxidative stress such as that caused by UV light, silica and infections, inhibit T cell DNA methylation and increase expression of genes such as CDI l a , perforin, CD70, CD40L and KIR genes, converting normal
Environmental agents associated with lupus alter the T cell epigenome, activating genes that convert normal T cells into autoreactive cells that cause lupus in mice. Similar changes characterize a T cell subset in patients with active lupus. This project characterizes the transcriptome and epigenome of this subset, with the goal of identifying targets for therapeutic approaches that eliminate or suppress the subset without affecting normal cells, improving the treatment of human lupus.