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Targeting endothelial CD146 attenuates neuroinflammation by limiting lymphocyte extravasation to the CNS.

Duan, Hongxia; Xing, Shu; Luo, Yongting; Feng, Liqun; Gramaglia, Irene; Zhang, Ying; Lu, Di; Zeng, Qiqun; Fan, Kelong; Feng, Jing; Yang, Dongling; Qin, Zhihai; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette and Yan, Xiyun (2013). Targeting endothelial CD146 attenuates neuroinflammation by limiting lymphocyte extravasation to the CNS. Scientific reports, 3, article no. 1687.

DOI (Digital Object Identifier) Link: https://doi.org/10.1038/srep01687
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Abstract

The ability to selectively block the entry of leukocytes into the central nervous system (CNS) without compromising the immune system is an attractive therapeutic approach for treating multiple sclerosis (MS). Using endothelial CD146-deficienct mice as a MS model, we found that endothelial CD146 plays an active role in the CNS-directed extravasation of encephalitogenic T cells, including CD146+ TH1 and TH17 lymphocytes. Moreover, treating both active and passive MS models with the anti-CD146 antibody AA98 significantly decreased the infiltrated lymphocytes in the CNS and decreased neuroinflammation. Interestingly, the ability of AA98 to inhibit the migration of CD146+ lymphocytes was dependent on targeting endothelial CD146, but not lymphocytic CD146. These results suggest a key molecular target located on the blood-brain barrier endothelium that mediates the extravasation of inflammatory cells into the CNS. In addition, our data suggest that the AA98 is a promising candidate for treating MS and other CNS autoimmune diseases.

Item Type: Journal Item
Copyright Holders: 2013, Rights Managed by Nature Publishing Group
ISSN: 2045-2322
Keywords: autoimmunity; blood–brain barrier; neuroimmunology; multiple sclerosis
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 39557
Depositing User: Ignacio A Romero
Date Deposited: 25 Feb 2014 13:42
Last Modified: 07 Dec 2018 10:21
URI: http://oro.open.ac.uk/id/eprint/39557
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