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Circ Res. 2017 May 26;120(11):1740-1753. doi: 10.1161/CIRCRESAHA.116.310054. Epub 2017 Apr 18.

Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver.

Author information

1
From the Cardiovascular Medicine Unit, Department of Medicine, Karolinska Insititutet, Karolinska University Hospital, Stockholm, Sweden.
2
From the Cardiovascular Medicine Unit, Department of Medicine, Karolinska Insititutet, Karolinska University Hospital, Stockholm, Sweden. Goran.Hansson@ki.se.

Abstract

RATIONALE:

The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T-cell differentiation remains unknown.

OBJECTIVE:

To investigate hepatic T-cell subsets upon hypercholesterolemia.

METHODS AND RESULTS:

We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor-β1 in the liver. Adoptive transfer experiments revealed that intrahepatically differentiated Treg cells relocated to the inflamed aorta in atherosclerosis-prone low-density lipoprotein receptor deficient (Ldlr-/-) mice. Moreover, hypercholesterolemia induced the differentiation of intrahepatic, but not intrasplenic, Th17 cells in wild-type mice, whereas the disrupted liver homeostasis in hypercholesterolemic Ldlr-/- mice led to intrahepatic Th1 cell differentiation and CD11b+CD11c+ leukocyte accumulation.

CONCLUSIONS:

Our results elucidate a new mechanism that controls intrahepatic T-cell differentiation during atherosclerosis development and indicates that intrahepatically differentiated T cells contribute to the CD4+ T-cell pool in the atherosclerotic aorta.

KEYWORDS:

atherosclerosis; hypercholesterolemia; inflammation; liver; metabolism; regulatory T-cells; transforming growth factor beta

PMID:
28420668
DOI:
10.1161/CIRCRESAHA.116.310054
[Indexed for MEDLINE]

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