Antibody mediated neutralization of myelin associated EphrinB3 accelerates CNS remyelination


Change log
Authors
Syed, Yasir A 
Zhao, Chao 
Mahad, Don 
Möbius, Wiebke 
Altmann, Friedrich 
Abstract

Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.

Description

This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s00401-015-1521-1

Keywords
Remyelination, EphrinB3, Oligodendrocytes, Multiple Sclerosis
Journal Title
Acta Neuropathologica
Conference Name
Journal ISSN
Volume Title
131
Publisher
Springer
Publisher DOI
Publisher URL
Sponsorship
This work was supported by the UK MS Society Grant ref: 941/11. MRNK held a NIHR Clinical Lectureship. KAN was supported by an ERC advanced award.