Beyond infection, systemic lupus erythematous (SLE) was the first human disease to be associated with increased type I interferon signaling36, and mutations in three distinct DNases, DNase I37, DNase III (TREX1)38 and DNase1L339, 40, have been reported to predispose to the development of lupus. Here, TREX1 is linked to systemic lupus erythematosus.