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EBI2 regulates intracellular signaling and migration in human astrocytes

Rutkowska, Aleksandra and Preuss, Inga and Gessier, Francois and Sailer, Andreas and Dev, Kumlesh (2015) EBI2 regulates intracellular signaling and migration in human astrocytes. Glia, 63 (2). pp. 341-351.

Abstract

The G protein-coupled receptor EBI2 (Epstein–Barr virus-induced gene 2) is activated by 7a, 25-dihydroxycholesterol (7a25HC) and plays a role in T cell-dependant antibody response and B cell migration. Aberrant EBI2 signaling is implicatedin a range of autoimmune disorders however its role in the CNS remains unknown. Here we characterize the functional role of EBI2 in GLIA cells using primary human astrocytes and EBI2 knockout animals. We find human and mouse astrocytes express EBI2 and the enzymes necessary for synthesis and degradation of 7a25HC. In astrocytes, EBI2 activation stimulates ERK phosphorylation, calcium signaling and induces cellular migration. These results, for the first time, demonstrate a role for EBI2 inastrocyte function and suggest that modulation of this receptor may be beneficial in neuroinflammatory disorders.

Item Type: Article
Keywords: EBI2, oxysterol, GPCR, astrocyte, neuroinflammation, demeylination
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/10685

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