1. Increased lymphocyte activation and atherosclerosis in CD47-deficient mice
- Author
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Anu Autio, Gurpanna Saggu, Francisco E. Velázquez, Sara Rattik, Petr Jarolim, Daniel Engelbertsen, Andrew H. Lichtman, Robin A. F. Verwilligen, Francis W. Luscinskas, Gail Newton, Erik A. Levinsohn, Marie A.C. Depuydt, and Huan Wang
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0301 basic medicine ,medicine.drug_class ,T-Lymphocytes ,lcsh:Medicine ,CD47 Antigen ,Lymphocyte Activation ,Monoclonal antibody ,Article ,Virus ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Leukocyte Trafficking ,medicine ,Animals ,CD90 ,Efferocytosis ,lcsh:Science ,Mice, Knockout ,Multidisciplinary ,Chemistry ,CD47 ,lcsh:R ,Dendritic Cells ,Chronic inflammation ,Atherosclerosis ,Flow Cytometry ,3. Good health ,Killer Cells, Natural ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Cancer research ,Female ,lcsh:Q ,030217 neurology & neurosurgery ,CD8 - Abstract
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-γ 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-γ+ NK cells were expanded in atherosclerotic aorta and that CD90+ NK cells produce more IFN-γ 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.
- Published
- 2019
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