Purpose of review: Advances in understanding the genetic and molecular basis of innate immune system activation and function have supported the hypothesis that type I interferons (IFN-I), the essential mediators of antiviral host defense, are central contributors to the pathogenesis of systemic lupus erythematosus (SLE). This review addresses the recent data that support the rationale for therapeutic targeting of the IFN-I pathway in SLE.
Recent findings: New insights into the mechanisms of cell-intrinsic innate immune system activation, driven by endogenous virus-like nucleic acids and potentially modified by environmental stressors, provide a model for the induction of IFN-I that may precede the clinically apparent autoimmunity in patients with lupus. Further amplification of IFN-α production, induced by nucleic-acid-containing immune complexes that activate endosomal Toll-like receptors, augments and sustains immune system activation, autoimmunity and tissue damage.
Summary: As demonstrated in the murine studies of persistent virus infection accompanied by sustained production of IFN-I, blockade of the IFN-I pathway may reverse the immune dysregulation and tissue damage that are the essential features of the immunopathogenesis of SLE. Recent research progress has identified numerous therapeutic targets, and specific candidate therapeutics relevant to the IFN-I pathway are under investigation.