Nestin(+) cells direct inflammatory cell migration in atherosclerosis

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) nestin(+) cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin(+) cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin(+) cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin(+) cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin(+) stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin(+) 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.