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

• Published in: Glia Vol. 70; no. 6; pp. 1191 - 1209
• Main Authors: Zveik, Omri, Fainstein, Nina, Rechtman, Ariel, Haham, Nitzan, Ganz, Tal, Lavon, Iris, Brill, Livnat, Vaknin‐Dembinsky, Adi
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2022; Wiley Subscription Services, Inc
• Subjects: Animals; Cell activation; Cell Differentiation - physiology; Cell proliferation; Central nervous system; Cerebrospinal fluid; CSF; Differentiation; Gene expression; Glial stem cells; Humans; Immune system; Immunity; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Mice; Multiple sclerosis; Multiple Sclerosis - pathology; Myelin Sheath - metabolism; Myelination; neuroimmunology; NF-κB protein; oligodendrocyte; Oligodendrocyte Precursor Cells - metabolism; Oligodendrocytes; Oligodendroglia - metabolism; OPC; Progenitor cells; remyelination; Remyelination - physiology; Tumor necrosis factor; Tumor necrosis factor-TNF; neuroimmunology; OPC; multiple sclerosis; CSF; oligodendrocyte; immunity; remyelination
• ISSN: 0894-1491; 1098-1136; 1098-1136
• DOI: 10.1002/glia.24165

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. Main Points Exposure of OPC to CSF from pMS patients impaired OPC differentiation and immune gene expression. CSF from pMS patients impedes OPCs' pro‐inflammatory activity, including a decrease in MHC‐II expression, TNF‐α secretion, T cell and NFκB activation.