DNA methylation modulates HERV-E expression in CD4+T cells from systemic lupus erythematosus patients

Background: Previous studies have reported that the DNA of T cells from systemic lupus erythematosus (SLE) patients contains global hypomethylation that may contribute to the development of SLE. Human endogenous retroviruses (HERVs) are encoded within the genomes of all higher eukaryotes and are of special interest where autoimmune disorders are concerned. Until recently, minimal effort has been made to identify specific HERVs associated with SLE and to explore their precise mechanism of expression. Objective: To examine the expression of HERVs associated with SLE and elucidate the effect of ultraviolet B (UVB) exposure on SLE-associated HERV expression in CD4+ T cells from patients with SLE. Methods: Fifteen patients with SLE and 10 healthy controls were enrolled in the study. The mRNA expression of selected HERVs and the methylation status of the long terminal repeats (LTRs) in SLE-related HERVs in CD4+ T cells were investigated. Furthermore, CD4+ T cells treated with 5-aza-deoxycytidine (5-aza C) and UVB were analyzed. Reverse-transcription PCR (RT-PCR), quantitative real-time PCR (qRT-PCR) and bisulfite sequencing analysis were employed. Results: HERV-E mRNA expression was higher in lupus CD4+ T cells than in cells from healthy controls, whereas the mRNA expression levels of HERV-K, HERV-K10 and HERV-W were comparable in SLE patients and healthy controls. Additionally, the HERV-E mRNA expression level was positively correlated with SLE disease activity. Furthermore, the HERV-E LTR methylation level was decreased and was negatively correlated to the HERV-E mRNA expression level in lupus CD4+ T cells. Finally, lupus CD4+ T cells showed markedly decreased HERV-E LTR2C methylation levels and increased HERV-E mRNA expression after treatment with 5-aza C or UVB. Conclusion: HERV-E is involved in the development of SLE. HERV-E transcription may be activated via inhibition of LTR methylation in lupus CD4+ T cells. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.