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

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

Author information

1
Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
2
Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
3
Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, SE-171 76, Stockholm, Sweden. Electronic address: reiner.mailer@ki.se.

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

[Indexed for MEDLINE]

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