Long interspersed nuclear elements (LINE-1): potential triggers of systemic autoimmune disease

Recent advances have identified immune complexes containing nucleic acids as stimuli for toll-like receptors and inducers of type I interferon (IFN). While a similar mechanism may serve to amplify immune system activation and production of inflammatory mediators in vivo in the context of systemic autoimmune diseases, the initial triggers of autoimmunity have not been defined. In this review, we describe a category of potential inducers of autoimmunity, the endogenous retroelements, with a particular focus on long interspersed nuclear elements (LINE-1, L1). Increased expression of L1 transcripts or decreased degradation of L1 DNA or RNA could provide potent stimuli for an innate immune response, priming of the immune system, and induction of autoimmunity and inflammation. Genomic and genetic variations among individuals, sex-related differences in L1 regulation, and environmental triggers are among the potential mechanisms that might account for increased L1 expression. Induction of type I IFN by L1-enriched nucleic acids through TLR-independent pathways could represent a first step in the complex series of events leading to systemic autoimmune disease.