Furthermore, the hypomethylated CpG in mtDNA binds to the N-terminal C-type leucine-rich repeats of TLR9 [42].Consistently, circulating mtDNA has been implicated in TLR9-dependent inflammatory pathology of diverse diseases such as rheumatoid arthritis, atherosclerosis, hypertension, acute liver injury and non-alcoholic steatohepatitis [43], suggesting that targeting mtDNA may represent an potentially effective strategy to combat TLR9-dependent inflammatory diseases. Here, TLR9 is linked to rheumatoid arthritis.