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  • Title: Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults.
    Author: Li Y, Zhao M, Hou C, Liang G, Yang L, Tan Y, Wang Z, Yin H, Zhou Z, Lu Q.
    Journal: Diabetes Res Clin Pract; 2011 Nov; 94(2):242-8. PubMed ID: 21864931.
    Abstract:
    Aberrant DNA methylation in T cells has been linked to pathogenesis of autoimmune diseases. To investigate genomic and gene-specific DNA methylation levels in CD4(+) T cells from patients with latent autoimmune diabetes in adults (LADA), and to investigate changes in the expression of genes that regulate methylation as well as the autoimmune-related gene FOXP3 in these patients. Global CD4(+) T cell DNA methylation was measured in 15 LADA patients and 11 healthy controls using a methylation quantification kit. mRNA levels of DNA methytransferases (DNMTs), methyl-DNA binding domain proteins (MBDs) and FOXP3 were measured by real time PCR. Methylation of a FOXP3 regulatory element region was determined by bisulphite genomic sequencing. Genomic DNA methylation in CD4(+) T cells from LADA patients was significantly increased compared to controls. DNMT3b mRNA levels were higher in CD4(+) T cells from LADA patients than in controls. DNMT3b expression positively correlated with global DNA methylation in LADA CD4(+) T cells. FOXP3 expression was decreased, and the FOXP3 promoter region was hypermethylated in CD4(+) T cells from LADA patients compared with controls. DNA methylation levels are altered in CD4(+) T cells from LADA patients, which may contribute to disease onset and progression by affecting the expression of autoimmune-related genes.
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