MMP-9 Shedding Releases Truncated CD73 from Astrocytes

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Author Info

Yuanyuan Bai Shumin Zhou Jie Guo Fanqiang Kong Song Chen Zhiyun Wang Guoping Liu

Corresponding Author

Guoping Liu
Department of Neurology, Tianjin first central hospital, Tianjin, China

A B S T R A C T

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.

Article Info

Article Type

Research Article

Publication history

Received: Sat 06, Jun 2020
Accepted: Tue 30, Jun 2020
Published: Wed 22, Jul 2020

Copyright

© 2023 Guoping Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.NNB.2020.03.02