Cerebrospinal fluid of progressive multiple sclerosis patients reduces differentiation and immune functions of oligodendrocyte progenitor cells

Omri Zveik, Nina Fainstein, Ariel Rechtman, Nitzan Haham, Tal Ganz, Iris Lavon, Livnat Brill, Adi Vaknin-Dembinsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Oligodendrocyte progenitor cells (OPCs) are responsible for remyelination in the central nervous system (CNS) in health and disease. For patients with multiple sclerosis (MS), remyelination is not always successful, and the mechanisms differentiating successful from failed remyelination are not well-known. Growing evidence suggests an immune role for OPCs, in addition to their regenerative role; however, it is not clear if this helps or hinders the regenerative process. We studied the effect of cerebrospinal fluid (CSF) from relapsing MS (rMS) and progressive MS (pMS) patients on primary OPC differentiation and immune gene expression and function. We observed that CSF from either rMS or pMS patients has a differential effect on the ability of mice OPCs to differentiate into mature oligodendrocytes and to express immune functions. CSF of pMS patients impaired differentiation into mature oligodendrocytes. In addition, it led to decreased major histocompatibility complex class (MHC)-II expression, tumor necrosis factor (TNF)-α secretion, nuclear factor kappa-B (NFκB) activation, and less activation and proliferation of T cells. Our findings suggest that OPCs are not only responsible for remyelination, but they may also play an active role as innate immune cells in the CNS.

Original languageAmerican English
Pages (from-to)1191-1209
Number of pages19
JournalGLIA
Volume70
Issue number6
DOIs
StatePublished - Jun 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. GLIA published by Wiley Periodicals LLC.

Keywords

  • CSF
  • OPC
  • immunity
  • multiple sclerosis
  • neuroimmunology
  • oligodendrocyte
  • remyelination

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