EBI2 Regulates Intracellular Signaling and Migration in Human Astrocyte

The G protein-coupled receptor EBI2 (Epstein-Barr virus-induced gene 2) is activated by 7, 25-dihydroxycholesterol (725HC) and plays a role in T cell-dependant antibody response and B cell migration. Aberrant EBI2 signaling is implicated in 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 725HC. In astrocytes, EBI2 activation stimulates ERK phosphorylation, Ca2+ signaling and induces cellular migration. These results, for the first time, demonstrate a role for EBI2 in astrocyte function and suggest that modulation of this receptor may be beneficial in neuroinflammatory disorders. GLIA 2015;63:341-351