title: IFN-γ-producing Th17 cells bias by HMGB1-T-bet/RUNX3 axis might contribute to progression of coronary artery atherosclerosis.
abstract: BACKGROUND
  IFN-γ-producing Th17 cells have been implicated in autoimmune disorders, but their properties in humans are known only partially. The molecular mechanisms and external factors that govern IFN-γ-producing Th17-cell bias are incompletely understood. The present work was to clarify whether (i) IFN-γ-producing Th17 cells are present in the peripheral circulation of patients with coronary atherosclerosis (CA); (ii) high mobility group box (HMGB)1 in circulation is associated with IFN-γ-producing Th17-cell bias.
  
  
  METHODS
  Thirty-six patients (17 females and 19 males; 45-84 years) diagnosed as having atherosclerosis after coronary angiography for suspected or known CA were included the study cohort. Samples of peripheral blood were collected from healthy volunteers and patients, and classical tests (flow cytometry, RT-qPCR) were used to measure blood components.
  
  
  CONCLUSIONS
  Our results clearly demonstrated that HMGB1 were up-regulated in different progressive CA patients: 5.38 ± 1.48 ng/ml, 6.30 ± 1.53 ng/ml and 5.86 ± 1.12 ng/ml vs1.45 ± 0.65 ng/ml for only atherosclerotic plaque (AP), atherosclerotic plaque and some plaque rupture, no thrombosis (PR), plaque rupture and accompanying thrombosis (TH) and volunteers, respectively, p < 0.05. The frequency of IFN-γ-producing Th17 cells was 2.33 ± 0.58%, 1.93 ± 0.2% and 2.21 ± 0.65% vs 0.38 ± 0.21% for AP, PR, TH and volunteers, p < 0.05, respectively. Furthermore, HMGB1 contributed to IFN-γ-producing Th17-cell bias by controlling expression of T-bet and RUNX3. We demonstrated, for the first time, that HMGB1 is a potential inducer of IFN-γ-producing Th17-cell bias, and that IFN-γ-producing Th17 cells might be one of the pathogenic factors in atherosclerosis.
authors.affiliation: The Central Laboratory, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China; Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China; Department of Laboratory Medicine, The Affiliated Jiangyin Hospital of Nanjing University of Chinese Medicine, Jiangyin, 214400, China.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, The Fourth Hospital of Shanxi, Xi'an, 710043, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ni
authors.affiliation: The Central Laboratory, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Shen
authors.affiliation: The Central Laboratory, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Xu
authors.affiliation: The Central Laboratory, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China. Electronic address: szl30@yeah.net.
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003328:Coronary Thrombosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D024243:HMGB1 Protein / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic; D034622:RNA Interference; D012422:Rupture, Spontaneous; D012720:Severity of Illness Index; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D000098815:T-bet Transcription Factor
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C573415:IFNG protein, human; C493729:Runx3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma
keywords: Atherosclerosis; HMGB1; IFN-γ-producing Th17