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GW24-e1722 FOXP3 demethylation as a means of identifying quantitative defects in regulatory T cells in acute coronary syndrome
  1. Lü Caixia,
  2. Cuntai Zhang
  1. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Abstract

Objectives The contribution of regulatory T cells (Tregs) to the pathogenesis of acute coronary syndrome (ACS) remains poorly understood. One core obstacleis the lack of Treg-specific markers. A highly conserved CpG enriched element in fork head box P3intron 1 (FOXP3 i l) is unmethylated only in Tregs, and measuring the unmethylation of FOXP3 i l can be used to identify the role of Tregs inclinical diseases. This study investigated whether analysing the demethylation status of FOXP3 i 1 is a more reliablemeans than using Treg-specific surface markers in ACS.

Methods We evaluated circulating Tregs percentages on different levels including cell frequencies (CD4+CD25highFOXP3+Tregs and CD4+CD25highCD45+naïve Tregs) or FOXP3mRNA, FOXP3 i 1 demethylation status and related cytokine secretion in 89 patients with ACS and 35 controls.

Results FOXP3i 1 demethylation assay showed that the amount of Tregs in ACS patients was significantly reduced than that in controls (p = 0.0005). However, flow cytometry analysis did not identify any reduction of CD4+CD25highFOXP3+Tregs in ACS patients. Notably, younger patients had higherpercentage of CD4+CD25highFOXP3+Tregs but decreased percentage of CD4+CD25highCD45+naïve Tregs than either controlsor older patients. Furthermore, a DNA hypomethylation agent increasedthe amount of CD4+CD25highFOXP3+Tregs and Tregs related cytokine IL-10 and suppressed the production of pro-inflammatory cytokin einterferon-γ by inducing FOXP3 i 1 demethylation in vitro.

Conclusions A quantitative defect of Tregs, suggestive of decreased peripheral tolerance, could be a potential hallmark of ACS disease. Targeting FOXP3 i l demethylation might elevate the inhibitory activity of Tregs in ACS.

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