| First Author | Zhao Y | Year | 2022 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 42 |
| Issue | 12 | Pages | e311-e326 |
| PubMed ID | 36252122 | Mgi Jnum | J:346549 |
| Mgi Id | MGI:7524086 | Doi | 10.1161/ATVBAHA.122.318226 |
| Citation | Zhao Y, et al. (2022) Specific Loss of ABCA1 (ATP-Binding Cassette Transporter A1) Suppresses TCR (T-Cell Receptor) Signaling and Provides Protection Against Atherosclerosis. Arterioscler Thromb Vasc Biol 42(12):e311-e326 |
| abstractText | 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(CD4-/CD4-)Ldlr(-/-)) were generated by multiple steps of (cross)-breedings among Abca1(flox/flox), 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, Abca1(CD4-/CD4-)Ldlr(-/-) mice showed significantly attenuated arterial accumulations of T cells and smaller atherosclerotic lesions than Abca1(+/+)Ldlr(-/-)controls, 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)-gamma 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. |
