In contrast, TNF, a key driver of RA, enhances mtDNA release and initiates a cGAS/STING-dependent IFN response in inflammatory arthritis (168), and prolonged TNF therapy induces the creation of high quantities of IFN-I via a mechanism that stimulates IRF1 and IRF3 (169, 170). This evidence concerns the gene IRF1 and rheumatoid arthritis.