Abstract

Recently, we have discovered that transcription factor IRF5 plays a direct role in establishing a pro-inflammatory phenotype of macrophages. Macrophages are immune cells that are essential for the initiation and resolution of pathogen- or tissue damage-induced inflammation. They demonstrate remarkable plasticity that allows them to efficiently respond to environmental signals and change their phenotype and physiology in response to cytokines and microbial signals.

We have demonstrated that IRF5 directs transcriptional activation of the majority of pro-inflammatory cytokines, chemokines and co-stimulatory molecules and begun to dissect the molecular mechanisms of IRF5 directed gene regulation. Moreover, genetic polymorphisms in the IRF5 gene, leading to increased IRF5 mRNA expression, are associated with a number of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, multiple sclerosis and inflammatory bowel disease.

Our current understanding of the molecular events in immune cells responsible for IRF5 pathogenic function during the inflammatory response will be discussed.