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Updated: Aug 25, 2025
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
Specific Loss of ABCA1 (ATP-Binding Cassette Transporter A1) Suppresses TCR (T-Cell Receptor) Signaling and Provides
Ying Zhao1, Lili Zhang1, Limin Liu1
1Department of Pathophysiology (Y.Z., L.Z., L.L., F.D., Y.Y., S.D.), Soochow Medical College of Soochow University, Suzhou, China.
Background:
ABCA1 (ATP-binding cassette transporter A1) mediates cholesterol efflux to apo AI to maintain cellular cholesterol homeostasis. The current study aims to investigate whether T-cell-specific deletion of ABCA1 modulates the phenotype/function of T cells and the development of atherosclerosis.
Methods:
Mice with T-cell-specific deletion of ABCA1 on low-density lipoprotein receptor knockout (Ldlr) background (Abca1) were generated by multiple steps of (cross)-breedings among Abca1, CD4-Cre, and Ldlr mice.
Results:
Deletions of ABCA1 greatly suppressed cholesterol efflux to apo AI but slightly reduced membrane lipid rafts on T cells probably due to the upregulation of ABCG1. Moreover, ABCA1 deficiency impaired TCR (T-cell receptor) signaling and inhibited the survival and proliferation of T cells as well as the formation of effector memory T cells. Despite the comparable levels of plasma total cholesterol after Western-type diet feeding, Abca1Ldlr-/- mice showed significantly attenuated arterial accumulations of T cells and smaller atherosclerotic lesions than Abca1Ldlrcontrols, which were associated with reduced surface CCR5 (CC motif chemokine receptor 5) and CXCR3 (CXC motif chemokine receptor 3), decreased antiapoptotic Bcl-2 (B-cell lymphoma 2) and Bcl-xL (B-cell lymphoma extra-large), and hampered abilities to produce IL (interleukin)-2 and IFN (interferon)-γ by ABCA1-deficient T cells.
Conclusions:
ABCA1 is essential for T-cell cholesterol homeostasis. Deletion of ABCA1 in T cells impairs TCR signaling, suppresses the survival, proliferation, differentiation, and function of T cells, thereby providing atheroprotection in vivo.
Insights
Deleting ABCA1 in T cells impairs their function and cholesterol regulation, leading to reduced atherosclerosis development in mice. This highlights ABCA1
Area of Science:
- Immunology
- Cardiovascular Biology
- Molecular Biology
Background:
- ATP-binding cassette transporter A1 (ABCA1) is crucial for cellular cholesterol homeostasis by mediating cholesterol efflux.
- T-cell function and its role in atherosclerosis are complex and influenced by cellular lipid metabolism.
Purpose of the Study:
- To investigate the impact of T-cell-specific ABCA1 deletion on T-cell phenotype and function.
- To determine the effect of T-cell ABCA1 deficiency on atherosclerosis development in vivo.
Main Methods:
- Generated mice with T-cell-specific ABCA1 deletion on an Ldlr knockout background.
- Analyzed T-cell signaling, survival, proliferation, and effector memory formation.
- Assessed atherosclerotic lesion development and T-cell infiltration in vivo.
Main Results:
- ABCA1 deficiency in T cells impaired cholesterol efflux and TCR signaling.
- T-cell survival, proliferation, and effector memory differentiation were suppressed.
- Mice with T-cell ABCA1 deletion exhibited reduced atherosclerotic lesions and T-cell accumulation in arteries.
Conclusions:
- ABCA1 is essential for maintaining cholesterol homeostasis in T cells.
- T-cell ABCA1 deletion impairs T-cell function and confers protection against atherosclerosis.
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