The interaction between environmental triggers and epigenetics in autoimmunity

Abstract

Systemic lupus erythematosus flares when genetically predisposed people encounter environmental agents that cause oxidative stress, such as infections and sunlight. How these modify the immune system to initiate flares is unclear. Drug induced lupus models demonstrate that CD4+ T cells epigenetically altered with DNA methylation inhibitors cause lupus in animal models, and similar T cells are found in patients with active lupus. How infections and sun exposure inhibit T cell DNA methylation is unclear. DNA methylation patterns are replicated each time a cell divides in a process that requires DNA methyltransferase one (Dnmt1), which is upregulated as cells enter mitosis, as well as the methyl donor S-adenosylmethionine, created from dietary sources. Reactive oxygen species that inhibit Dnmt1 upregulation, and a diet poor in methyl donors, combine to cause lupus in animal models. Similar changes are found in patients with active lupus, indicating a mechanism contributing to lupus flares.