Mirroring the DNA hypomethylation accompanying transformation of SFs to a pathogenic hyper-responsive phenotype in RA, CIA-SFs exhibit hypomethylated global DNA relative to those from naïve mice: such rewiring can be mimicked by sustained in vitro treatment of Naïve-SFs with either IL-17 or IL-1β (Fig 2A), cytokines that act on SFs to synergistically drive joint inflammation and damage [17, 18] and are suppressed by ES-62 in vivo [10]. The gene discussed is IL17A; the disease is rheumatoid arthritis.