Article Text

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


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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