SLE is the most studied autoimmune disease correlated with epigenetic modifications, a pattern of robust demethylation of interferon signature supporting a pathogenic role for neutrophils in lupus has been suggested, as well as a model whereby DNA from lupus neutrophils externalized by NETosis enhance type-I IFN production via TLR-9 stimulation by hypomethylated DNA (217). Here, TLR9 is linked to systemic lupus erythematosus.