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Article

EBI2 Is Temporarily Upregulated in MO3.13 Oligodendrocytes during Maturation and Regulates Remyelination in the Organotypic Cerebellar Slice Model

1
Department of Laboratory Medicine, Medical University of Gdańsk, 80-210 Gdańsk, Poland
2
Department of Anatomy and Neurobiology, Medical University of Gdańsk, 80-210 Gdańsk, Poland
3
Chemical Biology and Therapeutics/Disease Area X/Liver, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4056 Basel, Switzerland
4
School of Medicine, Trinity College Dublin, Dublin 2, Ireland
*
Author to whom correspondence should be addressed.
Academic Editor: José Luis Zugaza
Int. J. Mol. Sci. 2021, 22(9), 4342; https://doi.org/10.3390/ijms22094342
Received: 1 March 2021 / Revised: 12 April 2021 / Accepted: 20 April 2021 / Published: 21 April 2021
(This article belongs to the Special Issue Cell Signaling in Neurodegeneration 2.0)
The EBI2 receptor regulates the immune system and is expressed in various immune cells including B and T lymphocytes. It is also expressed in astrocytes in the central nervous system (CNS) where it regulates pro-inflammatory cytokine release, cell migration and protects from chemically induced demyelination. Its signaling and expression are implicated in various diseases including multiple sclerosis, where its expression is increased in infiltrating immune cells in the white matter lesions. Here, for the first time, the EBI2 protein in the CNS cells in the human brain was examined. The function of the receptor in MO3.13 oligodendrocytes, as well as its role in remyelination in organotypic cerebellar slices, were investigated. Human brain sections were co-stained for EBI2 receptor and various markers of CNS-specific cells and the human oligodendrocyte cell line MO3.13 was used to investigate changes in EBI2 expression and cellular migration. Organotypic cerebellar slices prepared from wild-type and cholesterol 25-hydroxylase knock-out mice were used to study remyelination following lysophosphatidylcholine (LPC)-induced demyelination. The data showed that EBI2 receptor is present in OPCs but not in myelinating oligodendrocytes in the human brain and that EBI2 expression is temporarily upregulated in maturing MO3.13 oligodendrocytes. Moreover, we show that migration of MO3.13 cells is directly regulated by EBI2 and that its signaling is necessary for remyelination in cerebellar slices post-LPC-induced demyelination. The work reported here provides new information on the expression and role of EBI2 in oligodendrocytes and myelination and provides new tools for modulation of oligodendrocyte biology and therapeutic approaches for demyelinating diseases. View Full-Text
Keywords: EBI2 receptor; remyelination; cell migration; chemotaxis; MO3.13 oligodendrocytes; receptor trafficking; organotypic slice model EBI2 receptor; remyelination; cell migration; chemotaxis; MO3.13 oligodendrocytes; receptor trafficking; organotypic slice model
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MDPI and ACS Style

Velasco-Estevez, M.; Koch, N.; Klejbor, I.; Laurent, S.; Dev, K.K.; Szutowicz, A.; Sailer, A.W.; Rutkowska, A. EBI2 Is Temporarily Upregulated in MO3.13 Oligodendrocytes during Maturation and Regulates Remyelination in the Organotypic Cerebellar Slice Model. Int. J. Mol. Sci. 2021, 22, 4342. https://doi.org/10.3390/ijms22094342

AMA Style

Velasco-Estevez M, Koch N, Klejbor I, Laurent S, Dev KK, Szutowicz A, Sailer AW, Rutkowska A. EBI2 Is Temporarily Upregulated in MO3.13 Oligodendrocytes during Maturation and Regulates Remyelination in the Organotypic Cerebellar Slice Model. International Journal of Molecular Sciences. 2021; 22(9):4342. https://doi.org/10.3390/ijms22094342

Chicago/Turabian Style

Velasco-Estevez, Maria, Nina Koch, Ilona Klejbor, Stephane Laurent, Kumlesh K. Dev, Andrzej Szutowicz, Andreas W. Sailer, and Aleksandra Rutkowska. 2021. "EBI2 Is Temporarily Upregulated in MO3.13 Oligodendrocytes during Maturation and Regulates Remyelination in the Organotypic Cerebellar Slice Model" International Journal of Molecular Sciences 22, no. 9: 4342. https://doi.org/10.3390/ijms22094342

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