IFN-γ-producing Th17 cells bias by HMGB1-T-bet/RUNX3 axis might contribute to progression of coronary artery atherosclerosis

Atherosclerosis. 2015 Dec;243(2):421-8. doi: 10.1016/j.atherosclerosis.2015.09.037. Epub 2015 Oct 3.

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.

Results and conclusion: 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.

Keywords: Atherosclerosis; HMGB1; IFN-γ-producing Th17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cells, Cultured
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / metabolism*
  • Coronary Thrombosis / blood
  • Coronary Thrombosis / diagnosis
  • Coronary Thrombosis / genetics
  • Coronary Thrombosis / immunology
  • Coronary Thrombosis / metabolism*
  • Disease Progression
  • Female
  • HMGB1 Protein / blood
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic
  • RNA Interference
  • Rupture, Spontaneous
  • Severity of Illness Index
  • Signal Transduction
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Transfection

Substances

  • Core Binding Factor Alpha 3 Subunit
  • HMGB1 Protein
  • HMGB1 protein, human
  • IFNG protein, human
  • Runx3 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interferon-gamma