title: Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults.
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.
authors.affiliation: Department of Endocrinology, Key Laboratory of Diabetes Immunology, Institute of Metabolism and Endocrinology, Diabetes Center, Second Xiangya Hospital, Central South University, Ministry of Education, Changsha, Hunan 410011, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Can
authors.initials: C
authors.lastname: Hou
authors.forename: Gongping
authors.initials: G
authors.lastname: Liang
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Tan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Yin
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D016022:Case-Control Studies; D002681:China; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C418974:FOXP3 protein, human