IRF5 as a Therapeutic Target for Lupus and Other Autoimmune Diseases

Failure of immunological tolerance due to genetic and environmental factors triggers autoimmunity. Among the diverse pathogenic mechanisms underlying autoimmune diseases, shared molecules that contribute to many conditions are potent therapeutic targets. Interferon regulatory factor 5 (IRF5) is a transcription factor that plays an essential role in the innate immune responses mediated by the Toll-like receptor-MyD88 innate immune signal transduction adaptor pathway. IRF5 undergoes several modulations in this pathway, including post-translational modification. IRF5 is implicated in the pathology of various autoimmune diseases such as systemic lupus erythematosus (SLE). Human genome-wide association studies have identified IRF5 gene polymorphisms that correlate with disease risk. Some polymorphisms have been shown to alter the expression of IRF5. Studies using mouse models have revealed the requirement of IRF5 in the pathogenesis of these disorders. Notably, the therapeutic effects of IRF5 inhibition have been demonstrated in mouse SLE models after disease onset. In this review, we summarize the findings of IRF5-driven pathogenesis of autoimmune diseases by presenting an overview of the polymorphisms of IRF5 which correlate with disease risk in humans and mouse models in which IRF5 has been implicated in autoimmune disease. Here, we discuss the potential of IRF5 as a novel therapeutic target for these diseases.