Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver
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Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver. / Mailer, Reiner K W; Gisterå, Anton; Polyzos, Konstantinos A; Ketelhuth, Daniel F J; Hansson, Göran K.
in: CIRC RES, Jahrgang 120, Nr. 11, 26.05.2017, S. 1740-1753.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver
AU - Mailer, Reiner K W
AU - Gisterå, Anton
AU - Polyzos, Konstantinos A
AU - Ketelhuth, Daniel F J
AU - Hansson, Göran K
N1 - © 2017 American Heart Association, Inc.
PY - 2017/5/26
Y1 - 2017/5/26
N2 - 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 hypercholesterolemicLdlr-/-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.
AB - 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 hypercholesterolemicLdlr-/-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.
KW - Animals
KW - Cell Differentiation
KW - Hypercholesterolemia
KW - Liver
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Random Allocation
KW - T-Lymphocytes, Regulatory
KW - Journal Article
U2 - 10.1161/CIRCRESAHA.116.310054
DO - 10.1161/CIRCRESAHA.116.310054
M3 - SCORING: Journal article
C2 - 28420668
VL - 120
SP - 1740
EP - 1753
JO - CIRC RES
JF - CIRC RES
SN - 0009-7330
IS - 11
ER -
