| First Author | Zhao M | Year | 2018 |
| Journal | Clin Immunol | Volume | 187 |
| Pages | 113-121 | PubMed ID | 29113828 |
| Mgi Jnum | J:278874 | Mgi Id | MGI:6356212 |
| Doi | 10.1016/j.clim.2017.11.002 | Citation | Zhao M, et al. (2018) Downregulation of BDH2 modulates iron homeostasis and promotes DNA demethylation in CD4(+) T cells of systemic lupus erythematosus. Clin Immunol 187:113-121 |
| abstractText | DNA hypomethylation plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4(+) T cells. Our results showed that BDH2 expression was decreased, intracellular iron was increased, global DNA hydroxymethylation level was elevated, while methylation level was reduced in lupus CD4(+) T cells compared with healthy controls. The decreased BDH2 contributed to DNA hyper-hydroxymethylation and hypomethylation via increasing intracellular iron in CD4(+) T cells, which led to overexpression of immune related genes. Moreover, we showed that BDH2 was the target gene of miR-21. miR-21 promoted DNA demethylation in CD4(+) T cells through inhibiting BDH2 expression. Our data demonstrated that the dysregulation of iron homeostasis in CD4(+) T cells induced by BDH2 deficiency contributes to DNA demethylation and self-reactive T cells in SLE. |
