title: DNA methylation modulates HERV-E expression in CD4+ T cells from systemic lupus erythematosus patients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhouwei
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Dermatology, The 309th Hospital of the Chinese People's Liberation Army, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Dermatology, Changzheng Hospital Affiliated with the Second Military Medical University, Shanghai, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China. Electronic address: shiweimin2@gmail.com.
authors.forename: Weimin
authors.initials: W
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D019175:DNA Methylation; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000532:radiotherapy / Q000821:virology; D008297:Male; D048348:Reverse Transcription / Q000235:genetics; D020079:Terminal Repeat Sequences / Q000235:genetics; D014467:Ultraviolet Therapy; D055815:Young Adult
keywords: Human endogenous retroviruses; Long terminal repeats; Methylation; Systemic lupus erythematosus; Ultraviolet B