Methylation of the FOXP3 upstream enhancer as a clinical indicator of defective regulatory T cells in patients with acute coronary syndrome.

Atherosclerosis is an immune-mediated inflammatory process, which acts as the main cause of acute coronary syndrome (ACS). Regulatory CD4+CD25+FOXP3+T cells (Tregs) are thought to play a major role in inhibiting the formation and progression of atherosclerosis. However, the exact role played by Tregs in the pathogenesis of ACS is yet remained unclear. FOXP3 is a key regulator of Treg formation and function. Demethylation at the CpG-rich island of FOXP3 upstream enhancers can alter FOXP3 expression, and may affect Treg function during the development of ACS. This study investigated the immunosuppressive function and methylation status of a FOXP3 upstream enhancer in Tregs in ACS patients. Notably, Tregs from ACS patients exhibited a significantly lower immunosuppressive effect on Teffs. Furthermore, the methylation status of the FOXP3 upstream enhancer was significantly increased in ACS patients. Consistent with these observations, Tregs originated from ACS patients manifested significantly lower levels of FOXP3 mRNA. The immunosuppressive effect of Tregs on Teffs was compromised in ACS patients. Together, our data suggest that examination of the methylation status of the FOXP3 upstream enhancer might be a novel approach to diagnose ACS and to differentiate ACS subtypes.