title: Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yuan
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.forename: Weiping
authors.initials: W
authors.lastname: Xu
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Zheng
authors.forename: Chaoyan
authors.initials: C
authors.lastname: Yue
authors.forename: Guanghui
authors.initials: G
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Yuan H
authors.initials: YH
authors.lastname: Yang
authors.forename: Michael P
authors.initials: MP
authors.lastname: Gantier
authors.forename: JunPing
authors.initials: J
authors.lastname: Liu
authors.forename: Dakang
authors.initials: D
authors.lastname: Xu
authors.forename: Lisong
authors.initials: L
authors.lastname: Shen
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human