Nestin(+) cells direct inflammatory cell migration in atherosclerosis

Abstract

Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestinþ cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestinþ cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestinþ cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestinþ cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestinþ stromal cells increase B30 times and contribute to the atheroma plaque. Mcp1 deletion in nestinþ cells—but not in endothelial cells only— increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis.