CD4⁺ and CD8⁺ T-Cell-Specific DNA Cytosine Methylation Differences Associated With Obesity

Lifestyle factors associated with obesity may alter epigenome-regulated gene expression. Most studies examining epigenetic changes in obesity have analyzed DNA 5´-methylcytosine (5mC) in whole blood, representing a weighted average of several distantly related and regulated leukocyte classes. To examine leukocyte-specific differences associated with obesity, a pilot study examining 5mC in three distinct leukocyte types isolated from peripheral blood of women with normal weight and obesity was conducted.

CD4⁺ T cells, CD8⁺ T cells, and CD16⁺ neutrophils were reiteratively isolated from blood, and 5mC levels were measured across >450,000 CG sites.

Nineteen CG sites were differentially methylated between women with obesity and with normal weight in CD4⁺ cells, 16 CG sites in CD8⁺ cells, and 0 CG sites in CD16⁺ neutrophils (q < 0.05). There were no common differentially methylated sites between the T-cell types. The amount of visceral adipose tissue was strongly associated with the methylation level of 79 CG sites in CD4⁺ cells, including 4 CG sites in CLSTN1's promoter, which, this study shows, may regulate its expression.

The methylomes of various leukocytes respond differently to obesity and levels of visceral adipose tissue. Highly significant differentially methylated sites in CD4⁺ and CD8⁺ cells in women with obesity that have apparent biological relevance to obesity were identified.