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J Neuroinflammation. 2017 Dec 16;14(1):250. doi: 10.1186/s12974-017-1025-0.

EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination.

Author information

1
Drug Development, School of Medicine, Trinity College, Dublin, Ireland. kowalcza@tcd.ie.
2
Medical University of Gdańsk, M. Skłodowskiej-Curie 3a, Gdańsk, Poland. kowalcza@tcd.ie.
3
Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
4
Drug Development, School of Medicine, Trinity College, Dublin, Ireland.

Abstract

BACKGROUND:

The G protein-coupled receptor EBI2 (Epstein-Barr virus-induced gene 2) is activated by 7α, 25-dihydroxycholesterol (7α25HC) and plays a role in T cell-dependant antibody response and B cell migration. Abnormal EBI2 signaling is implicated in a range of autoimmune disorders; however, its role in the CNS remains poorly understood.

METHODS:

Here we characterize the role of EBI2 in myelination under normal and pathophysiological conditions using organotypic cerebellar slice cultures and EBI2 knock-out (KO) animals.

RESULTS:

We find that MBP expression in brains taken from EBI2 KO mice is delayed compared to those taken from wild type (WT) mice. In agreement with these in vivo findings, we show that antagonism of EBI2 reduces MBP expression in vitro. Importantly, we demonstrate that EBI2 activation attenuates lysolecithin (LPC)-induced demyelination in mouse organotypic slice cultures. Moreover, EBI2 activation also inhibits LPC-mediated release of pro-inflammatory cytokines such as IL6 and IL1β in cerebellar slices.

CONCLUSIONS:

These results, for the first time, display a role for EBI2 in myelin development and protection from demyelination under pathophysiological conditions and suggest that modulation of this receptor may be beneficial in neuroinflammatory and demyelinating disorders such as multiple sclerosis.

KEYWORDS:

Demyelination; Epstein-Barr virus-induced gene 2 (EBI2 receptor); Multiple sclerosis; Myelination; Neuroinflammation; Organotypic slices

PMID:
29246262
PMCID:
PMC5732472
DOI:
10.1186/s12974-017-1025-0
[Indexed for MEDLINE]
Free PMC Article

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