An aggressive systemic lupus erythematosus (SLE)-like disease develops in mice following myeloid cell–specific deletion of Fas (CreLysMFasfl/fl) [9] or dendritic cell (DC)-specific deletion of caspase-8 (CreCD11cCasp8fl/fl) [10]. The gene discussed is CASP8; the disease is systemic lupus erythematosus.