DNA Methylation of CD4+ T-cells Reveals Association of ITGB7 in Pediatric Crohn’s Disease 公开
Shabazz, Kalifa (Fall 2020)
Published
Abstract
Crohn's Disease (CD) is a remitting and relapsing chronic inflammatory disorder of the gastrointestinal tract. Recently, we showed that peripheral blood cells of CD patients have distinct DNA methylation (DNAm) patterns related to inflammatory status. However, that study controlled for differences in cell composition between CD cases and controls, which prevented it from identifying cell type-specific changes. Mapping DNAm signatures to specific cell types during CD is fundamental in understanding the role of epigenetics in the onset and progression of disease. Therefore, we sought to distinguish cell type-specific composition and DNA methylation signatures during CD from bulk DNA that was isolated from blood samples and ileal biopsies obtained from CD pediatric patients and non-IBD controls (RISK cohort). Genome-wide DNAm was profiled using the MethylationEPIC array and TOols for the Analysis of heterogeneouS Tissues (TOAST) was used to test for cell-type specific DNAm differences in blood and ileal biopsies that associated with CD. The statistically significant sites were identified after multiple test correction with a false discovery rate of <0.05. In blood, CD cases had a higher proportion of neutrophils and a lower proportion of CD4+ T-cells relative to non-IBD controls. In CD4+ T-cells, methylation of cg04972065, in the intronic region of ITGB7, was lower in CD cases when compared to non-IBD controls. In ileal biopsies, we observed decreased expression of ITGB7 in cases when compared to non-IBD controls. Epigenetic regulation of CD4+ T-cells during CD leads to lower methylation of ITGB7, likely decreasing ITGB7 expression and regulating lymphocyte trafficking from the blood to and from gut-associated lymphoid tissues. Therefore, dysregulation of epigenetic factors affecting CD4+ T cell function may be a contributor to CD-associated gut inflammation.
Table of Contents
I. Introduction
II. Methods
III. Results
IV. Discussion
V. Figures 1-4
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DNA Methylation of CD4+ T-cells Reveals Association of ITGB7 in Pediatric Crohn’s Disease () | 2020-11-09 23:26:53 -0500 |
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