article = {NNB-2020-3-102}
title = {MMP-9 Shedding Releases Truncated CD73 from Astrocytes}
journal = {Neurology and Neurobiology}
year = {2020}
issn = {2613-7828}
doi = {http://dx.doi.org/10.31487/j.NNB.2020.03.02}
url = {https://www.sciencerepository.org/mmp-9-shedding-releases-truncated-cd73-from-astrocytes_NNB-2020-3-102 
author = {Yuanyuan  Bai,Shumin  Zhou,Jie  Guo,Fanqiang  Kong,Song  Chen,Zhiyun  Wang,Guoping  Liu,}
keywords = {Astrocytes, CD73, MMP-9, shedding}
abstract ={Previously we had reported that astrocytes physiologically express high levels of CD73 in their membrane,
converting extracellular AMP to immune suppressive adenosine, mediates an anti-inflammatory effect.
Following an interaction with effector T cells (CD4+CD25-
), astrocytes lost most of their membrane
expressed CD73, which rendered astrocytes’ immune suppressive function and accelerated neural
inflammation such as EAE. Here, we investigated the mechanism leading to the loss of membrane CD73 in
astrocytes. Our results revealed that there was no significant difference in Cd73 mRNA expressions between
CD73high and CD73low astrocytes. Membrane shedding of CD73 by matrix metalloproteinase-9 (MMP-9)
accounted for its membrane loss in astrocytes; meanwhile, C terminal truncated CD73 could be found in the
medium of induced CD73low astrocytes. With an MMP-9 inhibitor in existence, the shedding of CD73 in
wt-astrocytes, when interacted with CD73-/-
effector CD4 cells, was almost completely blocked, and the
production of pro-inflammatory cytokines, such as IL-17 and IFNγ, from interacted CD73-/-
effectors, were
significantly decreased. However, when a CD73 inhibitor was added together with MMP-9 inhibitor,
decreased production of pro-inflammatory cytokines were completely restored. As conclusion, our findings
suggested that under active inflammatory condition, MMP-9 releases CD73 from astrocytes. The block of
CD73 shedding in astrocytes by the addition of MMP-9 inhibitor could significantly decrease the activation
of interacted effector T cells.
}