Obesity promotes the global hypomethylation of CD4+ T cells in patients with systemic lupus erythematosus via downregulating DNMT1.

Abstract

The global hypomethylation of CD4+ T cells in systemic lupus erythematosus (SLE) patients has been previously reported. However, potential influencing factors are unclear. This study aimed to uncover the potential influence of obese on hypomethylated CD4+ T cells in SLE patients. Obese SLE patients with Body Mass Index (BMI)>30 (N.=15) and normal weight SLE patients with 18<BMI<25 (N.=20) were included. SLEADI, antinuclear-ribonuclear-protein (nRNP) and dsDNA levels in them were detected. Methylation rate of CD4+ T cells isolated from SLE patients was assessed, as well as its correlation to BMI and Systemic Lupus Erythematosus Disease Activity Index (SLEADI) in SLE patients. Subsequently, relative level and catalytic activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) were examined. New Zealand black/white (NZB/W) mice were fed high-fat diet for generating obesity model or normal diet, followed by detection of antinuclear-ribonuclear-protein (nRNP) immunoglobulin G (IgG), antidouble-stranded (ds) DNA IgG, methylation rate of CD4+ T cells and DNMT1 level. SLEADI, nRNP and dsDNA levels were higher in obese SLE patients than normal weight cases. SLEADI was positively correlated to BMI in included SLE patients. Compared with normal weight SLE patients, methylation rate of CD4+ T cells was lower in obese patients. DNMT1 was downregulated in obese SLE patients, and its level was negatively correlated to BMI in SLE patients. Consistently, methylation rate of CD4+ T cells and DNMT1 level remained lower in obese SLE mice than those normally fed mice with SLE. Hypomethylated CD4+ T cells extensively occur in SLE patients, which are much more pronounced in obese cases. DNMT1 level is found to be negatively correlated to the methylation rate of CD4+ T cells in SLE patients.