Unknown

Dataset Information

0

Increased lymphocyte activation and atherosclerosis in CD47-deficient mice.


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-? 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-?+ NK cells were expanded in atherosclerotic aorta and that CD90+ NK cells produce more IFN-? 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.

SUBMITTER: Engelbertsen D 

PROVIDER: S-EPMC6650435 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 kil  ...[more]

Similar Datasets

| S-EPMC2873333 | biostudies-literature
| S-EPMC2789234 | biostudies-literature
| S-EPMC5750111 | biostudies-literature
| S-EPMC2739759 | biostudies-literature
| S-EPMC5537437 | biostudies-other
| S-EPMC6113408 | biostudies-literature
| S-EPMC4831306 | biostudies-literature
| S-EPMC3384494 | biostudies-literature
| S-EPMC6989506 | biostudies-literature
| S-EPMC3151685 | biostudies-literature