TLRs and interferons: a central paradigm in autoimmunity

Investigations into the pathogenesis of lupus have largely focused on abnormalities in components of the adaptive immune system. Despite important advances, however, the question about the origin of the pathogenic process, the primary disease trigger, and the dominance of autoantibodies against nuclear components, remained unanswered. Discoveries in the last decade have provided some resolution to these questions by elucidating the central role of nucleic acid-sensing TLRs and the attendant inflammatory response, particularly the production of type I interferons. These priming events are responsible for initiating the adaptive responses that ultimately mediate the pathogenic process.