Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.
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 A...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3753235?pdf=render |
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| author | Yanhui Ma Xiangliang Yuan Lin Deng Weiping Xu Yingxia Zheng Chaoyan Yue Guanghui Zhang Fang Xie Yuan H Yang Michael P Gantier JunPing Liu Dakang Xu Lisong Shen |
| author_facet | Yanhui Ma Xiangliang Yuan Lin Deng Weiping Xu Yingxia Zheng Chaoyan Yue Guanghui Zhang Fang Xie Yuan H Yang Michael P Gantier JunPing Liu Dakang Xu Lisong Shen |
| author_sort | Yanhui Ma |
| collection | DOAJ |
| description | 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 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. 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. |
| first_indexed | 2024-12-22T09:35:51Z |
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| id | doaj.art-99f89deceb2249d2ae846277b240bf73 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T09:35:51Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-99f89deceb2249d2ae846277b240bf732022-12-21T18:30:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7280410.1371/journal.pone.0072804Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.Yanhui MaXiangliang YuanLin DengWeiping XuYingxia ZhengChaoyan YueGuanghui ZhangFang XieYuan H YangMichael P GantierJunPing LiuDakang XuLisong ShenAIMS: 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 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. 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.http://europepmc.org/articles/PMC3753235?pdf=render |
| spellingShingle | Yanhui Ma Xiangliang Yuan Lin Deng Weiping Xu Yingxia Zheng Chaoyan Yue Guanghui Zhang Fang Xie Yuan H Yang Michael P Gantier JunPing Liu Dakang Xu Lisong Shen Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling. PLoS ONE |
| title | Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling. |
| title_full | Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling. |
| title_fullStr | Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling. |
| title_full_unstemmed | Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling. |
| title_short | Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling. |
| title_sort | imbalanced frequencies of th17 and treg cells in acute coronary syndromes are mediated by il 6 stat3 signaling |
| url | http://europepmc.org/articles/PMC3753235?pdf=render |
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