Division of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA, USA.
Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Nat Rev Cardiol. 2020 Jul;17(7):387-401. doi: 10.1038/s41569-020-0352-5. Epub 2020 Mar 16.
Atherosclerosis is a chronic inflammatory disease of the arterial wall and the primary underlying cause of cardiovascular disease. Data from in vivo imaging, cell-lineage tracing and knockout studies in mice, as well as clinical interventional studies and advanced mRNA sequencing techniques, have drawn attention to the role of T cells as critical drivers and modifiers of the pathogenesis of atherosclerosis. CD4 T cells are commonly found in atherosclerotic plaques. A large body of evidence indicates that T helper 1 (T1) cells have pro-atherogenic roles and regulatory T (T) cells have anti-atherogenic roles. However, T cells can become pro-atherogenic. The roles in atherosclerosis of other T cell subsets such as T2, T9, T17, T22, follicular helper T cells and CD28 T cells, as well as other T cell subsets including CD8 T cells and γδ T cells, are less well understood. Moreover, some T cells seem to have both pro-atherogenic and anti-atherogenic functions. In this Review, we summarize the knowledge on T cell subsets, their functions in atherosclerosis and the process of T cell homing to atherosclerotic plaques. Much of our understanding of the roles of T cells in atherosclerosis is based on findings from experimental models. Translating these findings into human disease is challenging but much needed. T cells and their specific cytokines are attractive targets for developing new preventive and therapeutic approaches including potential T cell-related therapies for atherosclerosis.
动脉粥样硬化是动脉壁的一种慢性炎症性疾病,也是心血管疾病的主要潜在原因。来自体内成像、细胞谱系追踪和小鼠基因敲除研究的数据,以及临床介入研究和先进的 mRNA 测序技术,都引起了人们对 T 细胞作为动脉粥样硬化发病机制的关键驱动因素和调节因素的作用的关注。CD4 T 细胞通常存在于动脉粥样硬化斑块中。大量证据表明,辅助性 T 细胞 1(T1)细胞具有促动脉粥样硬化作用,调节性 T(Treg)细胞具有抗动脉粥样硬化作用。然而,T 细胞也可以变得促动脉粥样硬化。其他 T 细胞亚群如 T2、T9、T17、T22、滤泡辅助 T 细胞和 CD28 T 细胞以及其他 T 细胞亚群如 CD8 T 细胞和 γδ T 细胞在动脉粥样硬化中的作用尚未得到充分理解。此外,一些 T 细胞似乎具有促动脉粥样硬化和抗动脉粥样硬化的双重功能。在这篇综述中,我们总结了 T 细胞亚群及其在动脉粥样硬化中的功能以及 T 细胞归巢到动脉粥样硬化斑块的过程。我们对 T 细胞在动脉粥样硬化中的作用的认识很大程度上是基于实验模型的发现。将这些发现转化为人类疾病是具有挑战性的,但也是非常必要的。T 细胞及其特定细胞因子是开发新的预防和治疗方法的有吸引力的靶点,包括动脉粥样硬化的潜在 T 细胞相关治疗方法。