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Abstract
AimsExtensive evidence suggests inflammatory components participate in the pathogenic processes of acute coronary syndromes (ACS). In this study, we aimed to elucidate the role and mechanism underlying the imbalance of Th17 and Treg cell peripheral populations in the pathogenesis of ACS.Methods and ResultsUsing a flow cytometric analysis, we observed a significantly increased frequency of Th17 cells and a concurrently decreased CD4+CD25+Foxp3+ Treg cells in patients with ACS. To elucidate the mechanism of Th17/Treg imbalance in ACS, 22 inflammatory cytokines were measured using multiplexed immunobead-based assays. Of six elevated cytokines in ACS patients, only IL-6 was positively correlated with a higher Th17 cell level (r = 0.39, P<0.01). Relying on IL-6 stimulating and neutralizing studies, we demonstrated a direct role for IL-6 in sera from ACS patients with an increased frequency of Th17 cells. IL-6 induces the differentiation of Th17 cells from naïve CD4+ T cells through STAT3 activation and RORγt induction. However, we observed that high levels of TGF-β1 inhibited IL-6-dependent Th17 cell differentiation, indicating a complex interplay between the two cytokines in the control of Th17 and Treg cell populations.ConclusionsOur results demonstrate the role of IL-6-STAT3 signaling in ACS through increased Th17 cell differentiation. These findings indicate that IL-6 neutralizing strategies could present novel therapeutic avenues in the treatment of ACS.
Highlights
Extensive evidence supports a pathogenic role for both local and systemic inflammation in the origin and progression of atherosclerosis and in the pathogenesis of acute coronary syndromes (ACS) [1]
Our results demonstrate the role of IL-6-STAT3 signaling in ACS through increased Th17 cell differentiation
These findings indicate that IL-6 neutralizing strategies could present novel therapeutic avenues in the treatment of ACS
Summary
Extensive evidence supports a pathogenic role for both local and systemic inflammation in the origin and progression of atherosclerosis and in the pathogenesis of acute coronary syndromes (ACS) [1]. In addition to Th1 and Th2 cells, there is accumulating evidence for a critical role for Th17 and Treg cell subsets in the regulation of the immune system [2]. It has been proposed that increased Th17 cell levels correlate with decreased Treg cell levels, suggesting that the imbalance between these two subsets may contribute to the pathogenesis of atherosclerosis in humans [5]. The effects of such variation in the ratio of Th17/ Treg cells and the mechanisms underlying its imbalance effects in ACS remain poorly understood
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