A number of autoimmune diseases have an increased expression of type I interferon regulated genes in cells from peripheral blood and tissues. This so called interferon signature has been found in patients with SLE, primary Sjögrens syndrome, systemic sclerosis, myositis and a subset of patients with rheumatoid arthritis. The reasons behind the continuous activation of the type I interferon system in patients with these diseases are presence of self-derived inducers of type I interferon production by plasmacytoid dendritic cells (pDCs), lack of proper regulation of cells in the type I interferon system and a genetic predisposition to an enhanced type I interferon response. In fact, a large proportion of the genes predisposing to autoimmunity are involved in the type I interferon signaling pathway, either the production of type I interferon or the response downstream the type I interferon receptor. This has been extensively studied in SLE and among lupus risk genes involved in the production of type I interferon are interferon regulatory factor 5 (IRF5), IRF7 and interleukin-1 receptor associated kinase (IRAK1). SLE susceptibility genes important for the type I interferon response are tyrosine kinase 2 (Tyk2), Signal Transducer and Activator of Transcription 4 (STAT4) and interferon induced with helicase C domain 1 (Ifih1). Several of these genes are in addition risk genes for autoimmune diseases beside SLE. Rare mutations of a number of genes, for instance TREX1 and ACP5, also cause an increased expression of type I interferon stimulated genes and an autoimmune disease resembling SLE. There are several mechanism by which the increased activation of the type I interferon system can contribute to loss of tolerance and an autoimmune disease process. Thus, type I interferon is an immune adjuvant and stimulate cells in both the innate and adaptive immune system, but can also increase the expression of autoantigens. A major challenge in these so called type I interferonopathies is to down regulated the type I interferon system without increasing the risk for severe infections.

Disclosure of Interest None Declared