The role of IRF5 as an immune regulator

Abstract Interferon regulatory factor 5 (IRF5) is a transcription factor at the nexus of immune regulation, inflammation, and autoimmune disease. Studies have shown that dysregulation of IRF5 is strongly implicated in the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease. While originally described as a regulator downstream of Toll-like receptor (TLR)–MyD88 signaling in myeloid cells, further studies demonstrate a more complex role for IRF5 in mediating adaptive immune responses as well. In this review, we provide a summary of the role of IRF5 across the major immune cell populations in which it is expressed. We discuss the mechanistic basis of IRF5 function in each population, highlight shared themes, and examine the evidence supporting IRF5 as a promising therapeutic target whose inhibition may selectively dampen pathological inflammation while preserving protective immunity. We thus provide an overview of how IRF5 bridges both innate and adaptive immune responses.