LDL-reactive T-Zellen regulieren den Cholesterinspiegel und die Atheroskleroseentwicklung in humanisierten hypercholesterolemischen Mäusen,LDL-Reactive T Cells Regulate Plasma Cholesterol Levels and Development of Atherosclerosis in Humanized Hypercholesterolemic Mice.
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- Erscheinungsjahr:
- 2018
- Medientyp:
- Text
- Schlagworte:
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- Journal Article
- dk/atira/pure/keywords/workgroup/128
- SFB 841 "Leberentzündung: Infektion, Immunregulation und Konsequenzen" (128)
- dk/atira/pure/keywords/workgroup/132
- SFB 877 "Proteolysis as a Regulatory Event in Pathophysiology" (132)
- Beschreibung:
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BACKGROUND: Atherosclerotic cardiovascular disease is a chronic inflammatory process initiated when cholesterol-carrying low-density lipoprotein (LDL) is retained in the arterial wall. CD4+ T cells, some of which recognize peptide components of LDL as antigen, are recruited to the forming lesion, resulting in T-cell activation. Although these T cells are thought to be proatherogenic, LDL immunization reduces disease in experimental animals. These seemingly contradictory findings have hampered the development of immune-based cardiovascular therapy. The present study was designed to clarify how activation of LDL-reactive T cells impacts on metabolism and vascular pathobiology.
METHODS: We have developed a T-cell receptor-transgenic mouse model to characterize the effects of immune reactions against LDL. Through adoptive cell transfers and cross-breeding to hypercholesterolemic mice expressing the antigenic human LDL protein apolipoprotein B-100, we evaluate the effects on atherosclerosis.
RESULTS: A subpopulation of LDL-reactive T cells survived clonal selection in the thymus, developed into T follicular helper cells in lymphoid tissues on antigen recognition, and promoted B-cell activation. This led to production of anti-LDL immunoglobulin G antibodies that enhanced LDL clearance through immune complex formation. Furthermore, the cellular immune response to LDL was associated with increased cholesterol excretion in feces and with reduced vascular inflammation.
CONCLUSIONS: These data show that anti-LDL immunoreactivity evokes 3 atheroprotective mechanisms: antibody-dependent LDL clearance, increased cholesterol excretion, and reduced vascular inflammation.
- Lizenz:
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- info:eu-repo/semantics/openAccess
- Quellsystem:
- Forschungsinformationssystem des UKE
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- oai:pure.atira.dk:publications/8ee47bef-6e10-4e3d-9dfc-cb7b4b86aa9b