Abstract
BackgroundIncreased human endogenous retroviruses E clone 4–1 (HERV-E clone 4–1) mRNA expression is observed in systemic lupus erythematosus (SLE) patients and associates with the disease activity. In this study, we want to further investigate the mechanism of HERV-E clone 4–1 mRNA upregulation and its roles in SLE progression.MethodsCD4+ T cells were isolated from venous blood of SLE patients or healthy controls and qRT-PCR was used to detect HERV-E clone 4–1 mRNA expression. We then investigated the regulation of Nuclear factor of activated T cells 1 (NFAT1) and Estrogen receptor-α (ER-α) on HERV-E clone 4–1 transcription and the functions of HERV-E clone 4–1 3′ long terminal repeat (LTR) on DNA hypomethylation and IL-17 release.ResultsWe found HERV-E clone 4–1 mRNA expression was upregulated in CD4+ T cells from SLE patients and positively correlated with SLE disease activity. This is associated with the activation of Ca2+/calcineurin (CaN)/NFAT1 and E2/ER-α signaling pathway and DNA hypomethylation of HERV-E clone 4–1 5’LTR. HERV-E clone 4–1 also takes part in disease pathogenesis of SLE through miR-302d/Methyl-CpG binding domain protein 2 (MBD2)/DNA hypomethylation and IL-17 signaling via its 3’LTR.ConclusionsHERV-E clone 4–1 mRNA upregulation is due to the abnormal inflammation/immune/methylation status of SLE and it could act as a potential biomarker for diagnosis of SLE. HERV-E clone 4–1 also takes part in disease pathogenesis of SLE via its 3’LTR and the signaling pathways it involved in may be potential therapeutic targets of SLE.
Highlights
Increased human endogenous retroviruses E clone 4–1 (HERV-E clone 4–1) mRNA expression is observed in systemic lupus erythematosus (SLE) patients and associates with the disease activity
Enhanced expression of mRNA from Human endogenous retroviruses (HERV)-E clone 4–1 was reported in SLE than healthy controls (HCs) [5, 6], and our former study demonstrated that HERV-E clone 4– 1 mRNA expression was increased in SLE patients, and the expression level of HERV-E clone 4–1 was associated with SLE disease activity index (SLEDAI) [7]
HERV-E clone 4–1 mRNA expression was upregulated in CD4+ T cells from SLE patients In our former study, we found that HERV-E clone 4–1 mRNA expression was higher in lupus CD4+ T cells than in cells from healthy controls and the HERV-E clone 4–1 mRNA expression level was positively correlated with SLE disease activity [7]
Summary
Increased human endogenous retroviruses E clone 4–1 (HERV-E clone 4–1) mRNA expression is observed in systemic lupus erythematosus (SLE) patients and associates with the disease activity. Results: We found HERV-E clone 4–1 mRNA expression was upregulated in CD4+ T cells from SLE patients and positively correlated with SLE disease activity. This is associated with the activation of Ca2+/calcineurin (CaN)/NFAT1 and E2/ER-α signaling pathway and DNA hypomethylation of HERV-E clone 4–1 5’LTR. HERV-E clone 4–1 is inserted in the short arm of chromosome 19 at position 19p12 upstream of the ZNF66 gene locus and in the antisense orientation This full-length HERV-E clone 4–1 is considered to be an LTR2C prototype containing 5′ and 3′ LTR elements that are 95.5% identical and encompass gag, pol and env genes (GenBank: M10976, Additional file 1: Figure S1) [4]. HERV-E clone 4–1 5’LTR/LTR2C was hypomethylated in CD4+ T cells from SLE patients [7,8,9] which might have close relationship with its expression
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