Abnormal DNA methylation of ITGAL (CD11a) in CD4+ T cells from infants with biliary atresia.
Recent evidence indicates that alterations to epigenetic DNA methylation patterns contribute to many autoimmune diseases. Biliary atresia (BA) is a virus-induced autoimmune disease characterized by impaired T cells, which may be due to aberrant DNA methylation. CD11a, a subunit of the β2-integrin LFA-1 (CD11a/CD18) with costimulatory functions, is overexpressed due to hypomethylation of its promoter regulatory elements in CD4+ T cells from patients with many autoimmune diseases. However, it is unknown whether aberrant expression and methylation of CD11a occur in T cells from infants with BA. We aimed to compare the CD11a expression level and the methylation status of the CD11a promoter region in CD4+ T cells from BA infants and healthy controls (HC). We used real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to examine CD11a mRNA levels in CD4+ T cells from BA and HC infants. Bisulfite sequencing was used to determine the methylation status of the CD11a promoter and flanking regions in CD4+ T cells from BA and HC infants, and in CD4+ T cells with DNA methylation inhibitors. We found that CD11a expression is significantly decreased in BA CD4+ T cells (P=0.007). This was associated with hypermethylation of the CD11a promoter region in CD4+ T cells from infants with BA. Treatment with a DNA methylation inhibitor decreased CD11a promoter methylation and increased CD11a mRNA. Therefore, DNA hypermethylation at the CD11a locus contributes to the lowered expression of CD11a in BA CD4+ T cells.
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Rui
R
Dong
Rui
R
Zhao
Shan
S
Zheng
Yijie
Y
Zheng
Shudao
S
Xiong
Yiwei
Y
Chu
D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D001656:Biliary Atresia / Q000235:genetics / Q000276:immunology*; D040881:CD11a Antigen / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D040881:CD11a Antigen; D001374:Azacitidine