Abstract
The EBI2 receptor regulates the immune system and is expressed in various immune cells including B and T lymphocytes. It is also expressed in astrocytes in the central nervous system (CNS) where it regulates pro-inflammatory cytokine release, cell migration and protects from chemically induced demyelination. Its signaling and expression are implicated in various diseases including multiple sclerosis, where its expression is increased in infiltrating immune cells in the white matter lesions. Here, for the first time, the EBI2 protein in the CNS cells in the human brain was examined. The function of the receptor in MO3.13 oligodendrocytes, as well as its role in remyelination in organotypic cerebellar slices, were investigated. Human brain sections were co-stained for EBI2 receptor and various markers of CNS-specific cells and the human oligodendrocyte cell line MO3.13 was used to investigate changes in EBI2 expression and cellular migration. Organotypic cerebellar slices prepared from wild-type and cholesterol 25-hydroxylase knock-out mice were used to study remyelination following lysophosphatidylcholine (LPC)-induced demyelination. The data showed that EBI2 receptor is present in OPCs but not in myelinating oligodendrocytes in the human brain and that EBI2 expression is temporarily upregulated in maturing MO3.13 oligodendrocytes. Moreover, we show that migration of MO3.13 cells is directly regulated by EBI2 and that its signaling is necessary for remyelination in cerebellar slices post-LPC-induced demyelination. The work reported here provides new information on the expression and role of EBI2 in oligodendrocytes and myelination and provides new tools for modulation of oligodendrocyte biology and therapeutic approaches for demyelinating diseases.
Highlights
The Epstein–Barr virus-induced gene 2 (EBI2, GPR183) is highly expressed in the immune tissue and cells where it regulates innate and adaptive immune responses [1,2]. It is highly expressed in B and T lymphocytes and its signaling is implicated in a range of autoimmune diseases including type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis (MS) [3,4,5,6,7,8]
In addition to the studies investigating the effects of exogenously added 7α,25OHC on cellular chemotaxis in vitro, we demonstrated that macrophages migrate towards astrocyte-released 7α,25OHC [13]
EBI2 Receptor Is Expressed in OPCs in the Human Brain
Summary
The Epstein–Barr virus-induced gene 2 (EBI2, GPR183) is highly expressed in the immune tissue and cells where it regulates innate and adaptive immune responses [1,2]. It is highly expressed in B and T lymphocytes and its signaling is implicated in a range of autoimmune diseases including type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis (MS) [3,4,5,6,7,8]. Human and mouse astrocytes are the only brain-specific cells in which
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