Cause and consequences of the activated type I interferon system in SLE.
Patients with systemic lupus erythematosus (SLE) have an increased expression of type I interferon (IFN)-regulated genes (an IFN signature), which is caused by an ongoing production of type I IFNs by plasmacytoid dendritic cells (pDCs). The reasons behind the continuous IFN production in SLE are the presence of self-derived IFN inducers and a lack of negative feed-back signals that downregulate the IFN response. In addition, several cells in the immune system promote the IFN production by pDCs and gene variants in the type I IFN signaling pathway contribute to the IFN signature. The type I IFNs act as an immune adjuvant and stimulate T cells, B cells, and monocytes, which all play an important role in the loss of tolerance and persistent autoimmune reaction in SLE. Consequently, new treatments aiming to inhibit the activated type I IFN system in SLE are now being developed and investigated in clinical trials.
Department of Medical Sciences, Rheumatology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Maija-Leena
ML
Eloranta
Department of Medical Sciences, Rheumatology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. lars.ronnblom@medsci.uu.se.
Lars
L
Rönnblom
D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000276:immunology
D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta
Etiopathogenesis; Immune regulation; Plasmacytoid dendritic cells; Systemic lupus erythematosus; Type I interferon