title: Methylation of the FOXP3 upstream enhancer as a clinical indicator of defective regulatory T cells in patients with acute coronary syndrome.
abstract: 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.
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, China; Department of Cardiology, Xinyang Center HospitalXinyang 464000, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Geriatrics, Hebei Provincial People's Hospital Shijiazhuang 050000, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University Beijing 100029, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Bai
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ruang
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Cuntai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Quan
keywords: Acute coronary syndrome; DNA methylation; effector T cells; forkhead box P3; immunosuppressive function; regulatory T cells