| First Author | Engelbertsen D | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 10608 |
| PubMed ID | 31337788 | Mgi Jnum | J:285637 |
| Mgi Id | MGI:6387639 | Doi | 10.1038/s41598-019-46942-x |
| Citation | Engelbertsen D, et al. (2019) Increased lymphocyte activation and atherosclerosis in CD47-deficient mice. Sci Rep 9(1):10608 |
| abstractText | CD47, also known as integrin-associated protein (IAP), is a transmembrane protein with multiple biological functions including regulation of efferocytosis and leukocyte trafficking. In this study we investigated the effect of CD47-deficiency on atherosclerosis using a model of adeno-associated virus (AAV)-induced hypercholesterolemia. We observed increased plaque formation in CD47 null mice compared to wild-type controls. Loss of CD47 caused activation of dendritic cells, T cells and natural killer (NK) cells, indicating an important role for CD47 in regulating immunity. In particular, Cd47 deficiency increased the proportion of IFN-gamma producing CD90(+) NK cells. Treatment with depleting anti-NK1.1 monoclonal antibody (mAb), but not depleting anti-CD4/CD8 mAbs, equalized atherosclerotic burden, suggesting NK cells were involved in the enhanced disease in Cd47 deficient mice. Additional studies revealed that levels of CD90(+) and IFN-gamma(+) NK cells were expanded in atherosclerotic aorta and that CD90(+) NK cells produce more IFN-gamma than CD90(-) NK cells. Finally, we demonstrate that anti-CD47 (MIAP410) causes splenomegaly and activation of DCs and T cells, without affecting NK cell activation. In summary, we demonstrate that loss of CD47 causes increased lymphocyte activation that results in increased atherosclerosis. |
