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.Pro-CNIC FoundationSevero Ochoa Center of Excellence award SEV-2015-0505 to CNICWellcome Trust and MRC to the Cambridge Stem Cell InstituteMinisterio de Economía y Competitividad (RETIC Grant RD12/0042/0028 to V.A.; SAF2012-40127 to J.M-G.; Plan Nacional Grant SAF-2011-30308, Ramón y Cajal Program Grant RYC-2009-04703 and Spanish Cell Therapy Network TerCel to S.M-F.)Marie Curie Career Integration Program Grant (FP7-PEOPLE-2011-294096)ConSEPOC-Comunidad de Madrid Grant (S2010/BMD-2542)National Health Institute Blood and Transplant (United Kingdom)Horizon2020 (ERC-2014-CoG-64765)Horizon2020 (ERC-2014-CoG-64765
