Nucleic-acid mediated immunity

Mutant nucleases that mimics viral infection
Nucleic acids are potent activators of innate immunity. Innate immune sensing of nucleic acids provides resistance against viral infection and is important in the aetiology of autoimmune diseases.  Aicardi-Goutières syndrome (AGS) is an autoinflammatory disorder mimicking in utero viral infection of the brain and is inherited as an autosomal recessive trait. Phenotypically and immunologically it exhibits many similarities to Systemic Lupus Erythematosus (SLE). In recent years we have identified mutations for this disease in four genes that encode two nucleases. We hypothesise that in AGS and SLE, nucleic acid byproducts stimulate a chronic and inappropriate innate immune response. Given that AGS is a monogenic disorder with a defined molecular basis, we are using it as a model for common autoimmune disease to explore the cellular pathogenesis and molecular pathways implicated in nucleic acid triggered inflammatory responses. This should provide new insights into the aetiology of systemic autoimmune disease and immune-mediated damage of host by its inappropriate response to viral infection.