Increased expression of ephrins on immune cells of patients with relapsing remitting multiple sclerosis affects oligodendrocyte differentiation

Maya Golan, Avivit Krivitsky, Karin Mausner‐fainberg, Moshe Benhamou, Ifat Vigiser, Keren Regev, Hadar Kolb, Arnon Karni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of the inflammatory response on regenerative processes in the brain is complex. This complexity is even greater when the cause of the tissue damage is an autoimmune response. multiple sclerosis (MS) is an immune‐mediated disease in which demyelination foci are formed in the central nervous system. The degree of repair through oligodendrocyte regeneration and remyelination is insufficient. Ephrins are membrane‐bound ligands activating tyrosine kinase signaling proteins that are known to have an inhibitory effect on oligodendrocyte regeneration. In this study, we examined the expression of ephrins on immune cells of 43 patients with relapsing‐remitting (RR) MS compared to 27 matched healthy controls (HC). We found an increased expression of ephrin‐ A2, ‐A3 and ‐B3, especially on T cell subpopulations. We also showed overexpression of ephrins on immune cells of patients with RR‐MS that increases the forward signaling pathway and that expression of ephrins on immune cells has an inhibitory effect on the differentiation of oligodendrocyte precursor cells (OPCs) in vitro. Our study findings support the concept that the immune activity of T cells in patients with RR‐MS has an inhibitory effect on the differentiation capacity of OPCs through the expression and forward signaling of ephrins.

Original languageEnglish
Article number2182
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume22
Issue number4
DOIs
StatePublished - 2 Feb 2021

Funding

FundersFunder number
Roche Pharmaceuticals Ltd.

    Keywords

    • Ephrins
    • Multiple sclerosis
    • Oligodendrocyte differentiation
    • Oligodendrocyte precursor cells
    • T cells

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