Extracellular DNA-Triggered Inflammation in Arthritis

Cell-free DNA (cfDNA) comprises short fragments of double-stranded DNA, which promotes inflammation through various mechanisms. It can be detected in a variety of diseases, including autoimmune disorders like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), which has sparked interest for their potential use in diagnosis and therapy. Failure of clearance of extracellular DNA appears to be a major mechanism that may alter tissue homeostasis, leading to inflammation. In this review, we describe the characteristics of cfDNA, the role of bacterial-derived DNA in arthritis, and major sensing mechanisms by toll-like receptor 9 (TLR9). We aim to summarize up-to-date knowledge on the pathogenetic mechanisms of cfDNA in arthritis and discuss recent therapeutic approaches.