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Nestin(+) cells direct inflammatory cell migration in atherosclerosis.

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Del Toro, Raquel 
Chèvre, Raphael 
Rodríguez, Cristina 
Ordóñez, Antonio 
Martínez-González, José 


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.



Animals, Aorta, Apolipoproteins E, Atherosclerosis, Cell Movement, Chemokine CCL2, Diet, High-Fat, Endothelial Cells, Inflammation, Mesoderm, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes, Nestin, Neutrophils, Plaque, Atherosclerotic

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Nat Commun

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Springer Science and Business Media LLC
Medical Research Council (MC_PC_12009)
European Research Council (648765)
This work was supported by core support grants from the Pro-CNIC Foundation, Severo Ochoa Center of Excellence award SEV-2015-0505 to CNIC, and the Wellcome Trust and MRC to the Cambridge Stem Cell Institute, Spanish Ministry of Economy and Competitiveness (RETIC grant RD12/0042/0028 to VA; SAF2012-40127 to JM-G; Plan Nacional grant SAF-2011-30308, Ramón y Cajal Program grant RYC-2009-04703 and Spanish Cell Therapy Network TerCel to SM-F); Marie Curie Career Integration Program grant (FP7-PEOPLE-2011-294096) and ConSEPOC-Comunidad de Madrid grant (S2010/BMD-2542), National Health Institute Blood and Transplant (United Kingdom), Horizon2020 (ERC-2014-CoG-64765) and an International Early Career Scientist grant of the Howard Hughes Medical Institute to SM-F.