Neutrophils in patients with chronic coronary syndrome exhibit delayed apoptosis and resistance to regulatory T cell-induced apoptosis - Brief Report
BackgroundPersistent inflammation is linked to poor outcomes in patients with chronic coronary syndrome (CCS). The inflammatory state in atherosclerotic disease has been associated with activation of neutrophils as well as with regulatory T cell (Treg) deficiency. The role of Tregs in the regulation of neutrophil survival has been postulated recently. Here, we investigated neutrophil apoptosis along with the potential impact of Tregs on neutrophil apoptosis in patients with CCS, compared to healthy controls. MethodsTwenty patients with CCS and 19 healthy controls were included. Neutrophil apoptosis was assessed after 5h culture with or without interleukin(IL-)10, TNF or LPS. Neutrophil phenotype was evaluated through flow cytometry analysis of surface receptors (CD66b and CXCR4) and ex vivo release of cytokines and granule proteins. The ability of Tregs to induce neutrophil apoptosis was examined in autologous neutrophil-Treg co-cultures. ResultsSpontaneous neutrophil apoptosis was significantly delayed in patients compared to controls (10.3% vs. 19.2%, p=0.025). Also, neutrophils from patients overexpressed CD66b and CXCR4 and were more prone to release proinflammatory mediators. Notably, Tregs induced neutrophil apoptosis in healthy subjects, but not in patients, indicating a loss of Treg-mediated regulation in the latter. There was no evidence that IL-10 had any influence on neutrophil apoptosis. However, cell-to-cell contact was found essential for Treg-induced neutrophil apoptosis. ConclusionsPatients with CCS display delayed neutrophil apoptosis and a pro-inflammatory neutrophil phenotype that is resistant to Treg-mediated apoptosis. Neutrophil dysfunction may contribute to persistent inflammation in patients with CCS, and as such constitute a novel therapeutic target.