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Depletion of FOXP3(...
Depletion of FOXP3(+) regulatory T cells promotes hypercholesterolemia and atherosclerosis
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Klingenberg, Roland (author)
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Gerdes, Norbert (author)
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Badeau, Robert M (author)
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- Gisterå, Anton (author)
- Karolinska Institutet
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Strodthoff, Daniela (author)
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- Ketelhuth, Daniel FJ (author)
- Karolinska Institutet
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Lundberg, Anna M (author)
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- Rudling, Mats (author)
- Karolinska Institutet
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- Nilsson, Stefan K (author)
- Umeå universitet,Fysiologisk kemi
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- Olivecrona, Gunilla (author)
- Umeå universitet,Fysiologisk kemi
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Zoller, Stefan (author)
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Lohmann, Christine (author)
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Luescher, Thomas F (author)
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Jauhiainen, Matti (author)
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Sparwasser, Tim (author)
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- Hansson, Göran K (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2013
- 2013
- English.
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 123:3, s. 1323-1334
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Atherosclerosis is a chronic inflammatory disease promoted by hyperlipidemia. Several studies support FOXP3-positive regulatory T cells (Tregs) as inhibitors of atherosclerosis; however, the mechanism underlying this protection remains elusive. To define the role of FOXP3-expressing Tregs in atherosclerosis, we used the DEREG mouse, which expresses the diphtheria toxin (DT) receptor under control of the Treg-specific Foxp3 promoter, allowing for specific ablation of FOXP3(+) Tregs. Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3(+) Tregs. Depletion of Tregs caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. These mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. These results demonstrate that FOXP3(+) Tregs inhibit atherosclerosis by modulating lipoprotein metabolism.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Klingenberg, Rol ...
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Gerdes, Norbert
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Badeau, Robert M
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Gisterå, Anton
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Strodthoff, Dani ...
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Ketelhuth, Danie ...
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show more...
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Lundberg, Anna M
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Rudling, Mats
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Nilsson, Stefan ...
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Olivecrona, Guni ...
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Zoller, Stefan
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Lohmann, Christi ...
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Luescher, Thomas ...
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Jauhiainen, Matt ...
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Sparwasser, Tim
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Hansson, Göran K
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Other Basic Medi ...
- Articles in the publication
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Journal of Clini ...
- By the university
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Umeå University
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Karolinska Institutet