Emerging role of chemokine receptor 7 in atherosclerosis

Abstract

The CC chemokine receptor 7 (CCR7) and its ligands CCL19 and CCL21 essentially contribute to both immunity and tolerance by directing T cells and antigen-presenting dendritic cells (DCs) to and within lymph organs. In the pathogenesis of atherosclerosis, the accumulation of cholesterol in the subendothelial space of the vessel wall represents the initial step of plaque development in which DCs acquire and process low-density lipoprotein cholesterol as antigen in the vessel wall and then migrate to draining lymph nodes and present this antigen to naive T cells. Deletion of CCR7 receptor in murine atherosclerosis not only results in a reduced atherosclerotic plaque content but also leads to a disturbed entry and exit of T cells within the inflamed vessel wall. These observations are consistent with the notion that CCR7-dependent T cell priming in secondary lymphoid organs and CCR7-dependent recirculation of T cells between secondary lymphoid organs and inflamed tissue is pivotal for atherosclerotic plaque development and may represent an interesting target for innovative immune-modulatory therapy.