Demethylation of promoter regulatory elements contributes to CD70 overexpression in CD4<i>+</i> T cells from patients with subacute cutaneous lupus erythematosus

Abstract

BACKGROUND: Impaired methylation of T-cell DNA is thought to contribute to the development of systemic lupus erythematosus (SLE). CD70 (TNFSF7) is a B-cell costimulatory molecule that contributes to excessive B-cell stimulation in vitro and in vivo. CD70 is overexpressed in CD4+ T cells of patients with SLE, and DNA demethylation occurs in promoter sequences that regulate CD70 expression in SLE CD4+ T cells. However, it is unknown whether the expression and methylation of CD70 in CD4+ T cells are affected in patients with subacute cutaneous lupus erythematosus (SCLE). OBJECTIVE: To compare CD70 expression levels and the methylation status of the CD70 promoter region in CD4+ T cells from patients with SCLE and healthy controls. METHODS: We used real-time RT-PCR to compare messenger RNA levels of CD70 and flow cytometry to compare CD70 protein levels in CD4+ T cells from patients with SCLE and healthy controls. Bisulphite sequencing was used to determine the methylation status of the CD70 promoter region. RESULTS: CD70 is overexpressed at the surface of SCLE CD4+ T cells. Demethylation of the CD70 promoter region was seen in CD4+ T cells from patients with SCLE. CONCLUSIONS: Demethylation of regulatory elements contributes to CD70 overexpression in CD4+ T cells of patients with SCLE.