Activation-induced FOXP3 isoform profile in peripheral CD4+ T cells is associated with coronary artery disease

Atherosclerosis. 2017 Dec;267:27-33. doi: 10.1016/j.atherosclerosis.2017.10.026. Epub 2017 Oct 20.

Abstract

Background and aims: The expression of FOXP3 isoforms affects regulatory T (Treg) cell function. Reduced Treg cell function has been associated with coronary artery disease (CAD). However, alternative splicing of FOXP3 in CAD has not been investigated.

Methods: FOXP3 splice variants and IL17A transcripts in peripheral blood mononuclear cells from stable CAD patients and healthy controls were quantified, and FOXP3 isoform expression in response to T cell receptor (TCR) stimulation or LDL was analyzed by flow cytometry.

Results: Compared to healthy controls, CAD patients expressed significantly more FOXP3 transcripts that included exon 2, whereas alternative splicing of exon 7 in correlation with IL17A expression was reduced. Moreover, TCR stimulation, as well as exposure to LDL, decreased alternative splicing of FOXP3 in CD4+ T cells in vitro.

Conclusions: Our results demonstrate that blood mononuclear cells in stable CAD patients express a ratio of FOXP3 isoforms that is characteristic for activated CD4+ T cells.

Keywords: Alternative splicing; Coronary artery disease; FOXP3 isoforms; Treg cells.

MeSH terms

  • Adult
  • Aged
  • Alternative Splicing
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Case-Control Studies
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / metabolism*
  • Exons
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / blood
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / immunology
  • Humans
  • Interleukin-17 / blood
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Protein Isoforms
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Regulatory / immunology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL17A protein, human
  • Interleukin-17
  • Protein Isoforms
  • Receptors, Antigen, T-Cell