Peripheral Th17/Treg imbalance in patients with atherosclerotic cerebral infarction

Int J Clin Exp Pathol. 2013 May 15;6(6):1015-27. Print 2013.

Abstract

Objective: CD4(+)CD25(+) regulatory T (Treg) cells and Th17 cells play important roles in peripheral immunity. Oxidized low-density lipoprotein (ox-LDL) is an instrumental factor in atherogenesis. However, the changes of Th17/Treg cells in patients with acute cerebral Infarction (ACI) and impact on Th17/Treg by ox-LDL are not clear. Here, we examined the balance of Th17/Treg in ACI patients and the effect of ox-LDL on this balance.

Materials and methods: The frequencies of Th17 and Treg cells, key transcription factors and relevant cytokines were examined in patients with ACI, Transient ischemic attack (TIA) and controls. The correlations of cytokines, inflammatory biomarkers and ox-LDL in serum to Th17/Treg frequency, and the effects of ox-LDL on Th17/Treg cells in vitro were analyzed.

Results: ACI patients have shown a significant increase of Th17 frequency, RORγt expression and Th17 related cytokines (IL-17 and IL-6 ) levels, and a clear decline of Treg frequency, Foxp3 expression, suppressive function and regulatory cytokines (IL-10 and TGF-β1) levels. Furthermore, TIA patients also have notable variation as compared to control group. Serum ox-LDL and inflammatory biomarkers were positively correlated with the frequency of Th17 cells and negatively correlated with the frequency of Treg cells. Treg and Th17 cells from ACI patients were significantly susceptible to ox-LDL-mediated alterations in vitro.

Conclusions: Th17/Treg cells were imbalanced in ACI patients, and ox-LDL may contribute to this imbalance and lead to the occurrence of ACI suggesting their pathogenetic role in ACI.

Keywords: Cerebral infarction; T helper 17; atherosclerosis; oxidized low-density lipoprotein; regulatory T cells; transient ischemic attack.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cells, Cultured
  • Cerebral Infarction / blood
  • Cerebral Infarction / immunology*
  • Cerebral Infarction / pathology
  • Cytokines / blood
  • Female
  • Forkhead Transcription Factors / blood
  • Humans
  • Inflammation Mediators / blood
  • Intracranial Arteriosclerosis / blood
  • Intracranial Arteriosclerosis / immunology*
  • Intracranial Arteriosclerosis / pathology
  • Ischemic Attack, Transient / blood
  • Ischemic Attack, Transient / immunology*
  • Ischemic Attack, Transient / pathology
  • Lipoproteins, LDL / blood
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / blood
  • Prognosis
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*

Substances

  • Biomarkers
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Inflammation Mediators
  • Lipoproteins, LDL
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • oxidized low density lipoprotein