Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?
Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?
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DOI：
10.1160/th11-09-0605
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发表时间：
2011-11-01
影响因子：
6.7
通讯作者：
Zirlik, Andreas
中科院分区：
文献类型：
--
作者：
Gerdes, Norbert;Zirlik, Andreas
大量的基础实验室和临床研究已经揭示了动脉粥样硬化的慢性炎症本质。适应性免疫系统及其领跑者T细胞在所有阶段驱动动脉粥样硬化过程。T细胞功能依赖于多种共刺激或共抑制信号并受其控制。此外，这些蛋白质中的许多在多种细胞类型上包合不依赖于T细胞的促动脉粥样硬化功能。因此，它们代表了动脉粥样硬化的免疫调节和/或抗炎治疗的潜在靶点。本文综述了B7和肿瘤坏死因子（TNF）超家族共刺激分子及其下游信号效应子在动脉粥样硬化中的不同作用。特别是CD 28/CD 80/CD 86/CTLA 4、ICOS/ICOSL、PD-1/PDL-1/2、TRAF、CD 40/CD 154、OX 40/OX 40 L、CD 137/CD 137 L、CD 70/CD 27、GITR/GITRL和LIGHT在动脉疾病中的作用。最后，讨论了这些分子在动脉粥样硬化治疗中的治疗开发潜力。
A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune-modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed.