ABCA1（ATP 结合盒转运体 A1）特异性缺失对 TCR（T 细胞受体）信号的抑制及其抗动脉粥样硬化保护作用

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.

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.

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)- by ABCA1-deficient T cells.

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.