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EBI2 is expressed in glial cells in multiple sclerosis lesions and its knock-out modulates remyelination in the cuprizone model

Klejbor, I, Shimshek, Derya, Klimaszewska-Łata, J, Velasco-Estevez, M, Moryś, J, Karaszewski, B, Szutowicz, A and Rutkowska, A (2021) EBI2 is expressed in glial cells in multiple sclerosis lesions and its knock-out modulates remyelination in the cuprizone model. European Journal of Neuroscience. ISSN 0953-816X1460-9568


EBI2 receptor regulates the immune system and in multiple sclerosis is upregulated in the central nervous system infiltrating lymphocytes. In newborn EBI2-deficient mice, myelin development is delayed and its persistent antagonism inhibits remyelination in chemically-demyelinated organotypic cerebellar slices. We used the cuprizone model of multiple sclerosis to elucidate the role of central nervous system-expressed EBI2 in de- and remyelination. The wild-type and EBI2 knock-out mice were fed 0.2% cuprizone in chow for five weeks and allowed to recover on a normal diet for two weeks. The data showed less efficient recovery of myelin, attenuated oligodendrocyte loss, fewer astrocytes and increased total cholesterol levels in the EBI2 knock-out mice after recovery. Moreover, the wild-type mice upregulated EBI2 expression after recovery confirming the involvement of EBI2 signalling during recovery from demyelination in the cuprizone model. The pro-inflammatory cytokine levels were at comparable levels in the wild-type and EBI2 knock-out mice, with only minor differences in TNFα and IL1β levels either at peak or during recovery. The neuroinflammatory signalling molecules, Abl1 kinase and NFКB1 (p105/p50) subunit, were significantly downregulated in the EBI2 knock-out mice at peak of disease. Immunohistochemical investigations of EBI2 receptor distribution in the CNS cells in MS brain revealed strong expression of EBI2 in astrocytes and microglia inside the plaques implicating glia-expressed EBI2 in multiple sclerosis pathophysiology. Taken together, these findings demonstrate the involvement of EBI2 signalling in the recovery from demyelination rather than in demyelination and as such warrant further research into the role of EBI2 in remyelination.

Item Type: Article
Keywords: cuprizone model demyelination EBI2 receptor GPR183 multiple sclerosis neuroinflammation remyelination
Date Deposited: 21 Jul 2021 00:45
Last Modified: 21 Jul 2021 00:45


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