Model of key events in SLE pathogenesis. Dying cells release nucleic acid, including DNA, which binds immunoglobulin to form circulating immune complexes. These immune complexes can directly mediate cell damage by binding to target tissues, for example in the glomerulus. Immune complexes also bind Fc receptors on plasmacytoid dendritic cells, and in concert with RAGE receptors and TLR9, promote expression and release of IFN-α. IFN-α, in turn, promotes multiple immune system aberrations including the upregulation of B cells, T cells, and dendritic and endothelial cells. RAGE, receptor for advanced glycation end-products; SLE, systemic lupus erythematosus; TLR, Toll-like receptor.