Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease characterized by a large number of aberrations in the immune system, typically resulting in the formation of autoantibodies against nucleic acid and associated proteins. In order to better understand the disease mechanisms and develop efficient therapies for SLE, new technologies such as microarray analysis have been applied to cells and tissues from patients with SLE. Studies of the gene expression profile in SLE have revealed that the majority of patients have the dominant pattern of type I interferon (IFN)–inducible gene expression, commonly referred to as an IFN signature (1, 2). These discoveries are consistent with earlier observations that patients with SLE have increased serum levels of IFN and cellular expression of the IFN-inducible protein MxA (3). The observation that an SLE syndrome can develop during longterm IFN treatment of patients with chronic infections and malignant diseases (4) further supports a critical role for the type I IFN system in the etiopathogenesis of SLE (5, 6).

Several investigations also suggest that type I IFNs may be important in autoimmune diseases other than SLE and point to the possibility that the type I IFN system is a key actor when tolerance is lost and autoreactivity appears. Here, we present a short overview of