Role of DNA/RNA sensors and contribution to autoimmunity

Innate immune detection and subsequent immune responses rely on the initial recognition of pathogen specific molecular motifs. Foreign nucleic acids are key structures recognised by the immune system, recognition of which occurs mainly through the use of nucleic acid receptors including members of the Toll-like receptors, AIM2-like receptors, RIG-I-like receptors and intracellular DNA receptors. While the immune system is critically important in protecting the host from infection, it is of utmost importance that it is tightly regulated, in order to prevent recognition of self-nucleic acids and the subsequent development of autoimmunity. Defects in the mechanisms regulating such pathways, for example mutations in endonucleases that clear DNA, altered expression of nucleic acid sensors and defects in negative regulators of these signalling pathways involved in RNA/DNA sensing, have all been implicated in promoting the generation of autoimmune responses. This evidence, as reviewed here, suggests that novel therapeutics targeting these sensors and their downstream pathways may be of use in the treatment of patients with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome.