Increased lymphocyte activation and atherosclerosis in CD47-deficient mice

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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.


  • Daniel Engelbertsen
  • Anu Autio
  • Robin A.F. Verwilligen
  • Marie A.C. Depuydt
  • Gail Newton
  • Sara Rattik
  • Erik Levinsohn
  • Gurpanna Saggu
  • Petr Jarolim
  • Huan Wang
  • Francisco Velazquez
  • Andrew H. Lichtman
  • Francis W. Luscinskas
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • Brigham and Women's Hospital / Harvard Medical School

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
TidskriftScientific Reports
Utgåva nummer1
StatusPublished - 2019 jul 23
Peer review utfördJa