| First Author | Li H | Year | 2018 |
| Journal | JCI Insight | Volume | 3 |
| Issue | 16 | PubMed ID | 30135300 |
| Mgi Jnum | J:288045 | Mgi Id | MGI:6407477 |
| Doi | 10.1172/jci.insight.120880 | Citation | Li H, et al. (2018) Precision DNA demethylation ameliorates disease in lupus-prone mice. JCI Insight 3(16) |
| abstractText | 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-alphabeta+CD4-CD8- double-negative T cells. Our results signify the importance of cell-specific inhibition of DNA methylation in the treatment of established lupus. |
