Downregulation of BDH2 modulates iron homeostasis and promotes DNA demethylation in CD4+ T cells of systemic lupus erythematosus

作者：Zhao, Ming^*; Li, Meng-ying; Gao, Xiao-fei; Jia, Su-jie; Gao, Ke-qin; Zhou, Yin; Zhang, Hui-hui; Huang, Yi; Wang, Jing; Wu, Hai-jing; Lu, Qian-jin^*

来源：Clinical Immunology, 2018, 187: 113-121.

DOI：10.1016/j.clim.2017.11.002

• Systemic lupus erythematosus
• T cells
• DNA methylation
• DNA hydroxymethylation
• Iron homeostasis

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 homeo-stasis, 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.

• 出版日期2018-2
• 单位中南大学