TY - JOUR AU - Li, Hao AU - Tsokos, Maria G. AU - Bickerton, Sean AU - Sharabi, Amir AU - Li, Yi AU - Moulton, Vaishali R. AU - Kong, Philip AU - Fahmy, Tarek M. AU - Tsokos, George C. T1 - Precision DNA demethylation ameliorates disease in lupus-prone mice PY - 2018/08/23/ AB - Defective DNA methylation in T cells leads to a series of T cell abnormalities in lupus; however, the full effect of T cell lineage–specific DNA methylation on disease expression has not been explored. Here, we show that 5-azacytidine, a DNA methyltransferase inhibitor, targeted to either CD4 or CD8 T cells in mice with established disease using a nanolipogel delivery system dramatically ameliorates lupus-related pathology through distinct mechanisms. In vivo targeted delivery of 5-azacytidine into CD4 T cells favors the expansion and function of Foxp3+ Tregs, whereas targeted delivery to CD8 T cells enhances the cytotoxicity and restrains the expansion of pathogenic TCR-αβ+CD4–CD8– double-negative T cells. Our results signify the importance of cell-specific inhibition of DNA methylation in the treatment of established lupus. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.120880 VL - 3 IS - 16 UR - https://doi.org/10.1172/jci.insight.120880 PB - The American Society for Clinical Investigation ER -