Changes in IL-27 and its effect on CD4 + T cells in patients with coronary artery disease

Abstract

Objective：Coronary artery disease (CAD) is an immune-mediated chronic disease, and interleukin-27(IL-27) regulates CD4+ T cell differentiation. However, little is known about its effects on CAD. Therefore, we aimed to investigate the changes of IL-27 and its effect on CD4+ T cells in patients with CAD.Methods: The severity of coronary artery stenosis was assessed by Gensini score, and the concentrations of plasma IL-27, ox-LDL were measured by ELISA. qRT-PCR and Western Blotting (WB) were performed to evaluate the mRNA and protein expression of T-bet, IFN-γ, GATA-3, and RORγt. After monocytes were stimulated with recombinant IL-2 and/or IL-27, CD4+IFN-γ+T cells, CD4+IL-4+T cells, CD4+IL-17+T cells, CD4+LAP+T cells and CD4+CD25+Foxp3+ Tregs were counted by flow cytometry. Results: Plasma IL-27 levels were significantly elevated in patients with Acute Coronary Syndromes (ACS). IL-27 levels were positively correlated with ox-LDL and Gensini scores (P < 0.01) and ox-LDL levels were positively correlated with Gensini scores (P < 0.01). The more severe the stenosis in CAD patients, the more Th1 and Th17 cells, and the less Th2, CD4+CD25+Foxp3+Tregs and CD4+LAP+T cells. IL-27 can increase the expression of T-bet and IFN-γ, and inhibit the expression of RORγt and GATA-3, and finally promote the differentiation of CD4+T cells into Th1 cells, and inhibit the differentiation of Th2, Th17, CD4+CD25+Foxp3+Tregs and CD4+LAP+T cells.Conclusion: IL-27 regulates CAD by increasing the expression of T-bet and IFN-γ and inhibiting the expression of RORγt and GATA-3, thereby increasing the frequency of Th1 cells and decreasing the frequency of Th2, Th17, CD4+CD25+Foxp3+Tregs and CD4+LAP+T cells.