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.