Dataset Information

Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.

ABSTRACT:

Aims

Extensive 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 results

Using 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 ROR?t induction. However, we observed that high levels of TGF-?1 inhibited IL-6-dependent Th17 cell differentiation, indicating a complex interplay between the two cytokines in the control of Th17 and Treg cell populations.

Conclusions

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.

SUBMITTER: Ma Y

PROVIDER: S-EPMC3753235 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.

Ma Yanhui Y Yuan Xiangliang X Deng Lin L Xu Weiping W Zheng Yingxia Y Yue Chaoyan C Zhang Guanghui G Xie Fang F Yang Yuan H YH Gantier Michael P MP Liu JunPing J Xu Dakang D Shen Lisong L

PloS one 20130826 8

<h4>Aims</h4>Extensive 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.<h4>Methods and results</h4>Using 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 ...[more]

PMID: 23991153

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Project description:Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS).To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates.A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina.Thirty-day mortality following ACS.Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70).Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease.

Dataset Information

Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.

Aims

Methods and results

Conclusions

Publications

Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.

Similar Datasets

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