Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults

Diabetes Res Clin Pract. 2011 Nov;94(2):242-8. doi: 10.1016/j.diabres.2011.07.027. Epub 2011 Aug 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / chemistry*
  • CD4-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • China
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation*
  • DNA Methyltransferase 3A
  • DNA-Binding Proteins / genetics
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Real-Time Polymerase Chain Reaction

Substances

  • DNA-Binding Proteins
  • DNMT3A protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • RNA, Messenger
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNA methyltransferase 3B