Advanced

Increased lymphocyte activation and atherosclerosis in CD47-deficient mice

Engelbertsen, Daniel LU ; Autio, Anu; Verwilligen, Robin A.F.; Depuydt, Marie A.C.; Newton, Gail; Rattik, Sara LU ; Levinsohn, Erik; Saggu, Gurpanna; Jarolim, Petr and Wang, Huan, et al. (2019) In Scientific Reports 9(1).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85069716324
ISSN
2045-2322
DOI
10.1038/s41598-019-46942-x
language
English
LU publication?
yes
id
1ad09d78-c924-480b-9e03-ec228b28a208
date added to LUP
2019-08-02 09:20:14
date last changed
2019-10-15 07:11:48
@article{1ad09d78-c924-480b-9e03-ec228b28a208,
  abstract     = {<p>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<sup>+</sup> 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<sup>+</sup> and IFN-γ<sup>+</sup> NK cells were expanded in atherosclerotic aorta and that CD90<sup>+</sup> NK cells produce more IFN-γ than CD90<sup>-</sup> 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.</p>},
  articleno    = {10608},
  author       = {Engelbertsen, Daniel and Autio, Anu and Verwilligen, Robin A.F. and Depuydt, Marie A.C. and Newton, Gail and Rattik, Sara and Levinsohn, Erik and Saggu, Gurpanna and Jarolim, Petr and Wang, Huan and Velazquez, Francisco and Lichtman, Andrew H. and Luscinskas, Francis W.},
  issn         = {2045-2322},
  language     = {eng},
  month        = {07},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Increased lymphocyte activation and atherosclerosis in CD47-deficient mice},
  url          = {http://dx.doi.org/10.1038/s41598-019-46942-x},
  volume       = {9},
  year         = {2019},
}