Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Daniel Engelbertsen

Assistant researcher

Default user image.

Increased lymphocyte activation and atherosclerosis in CD47-deficient mice

Author

  • 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

Summary, in English

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.

Department/s

  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2019-07-23

Language

English

Publication/Series

Scientific Reports

Volume

9

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Cardiovascular Research - Cellular Metabolism and Inflammation

ISBN/ISSN/Other

  • ISSN: 2045-2322