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EBI2 regulates pro-inflammatory signaling and cytokine release in astrocytes

Rutkowska, Aleksandra and Shimshek, Derya and Sailer, Andreas and Dev, Kumlesh (2018) EBI2 regulates pro-inflammatory signaling and cytokine release in astrocytes. Journal of neuroinflammation, 133. pp. 121-128. ISSN 0028-3908

Abstract

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 signalling is implicated in a range of autoimmune disorders however its role in the CNS remains poorly understood. 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. 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. 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.

Item Type: Article
Date Deposited: 08 May 2018 00:45
Last Modified: 08 May 2018 00:45
URI: https://oak.novartis.com/id/eprint/34708

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