INTRODUCTION: Epstein-Barr virus-induced gene 2 (EBI2) and its oxysterol ligand 7α,25-dihydroxycholesterol (7α,25OHC) play a critical role in immune cell migration and have been implicated in neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). EBI2 is expressed in various immune cells such as B and T cells, dendritic cells, natural killer cells as well as in microglia, astrocytes and oligodendrocytes. In the CNS, EBI2 is upregulated in infiltrating glial cells. Astrocytes and microglia produce oxysterols in response to inflammatory stimuli and facilitate astrocyte-macrophage communication. EBI2 is also transiently upregulated during oligodendrocyte maturation, and 7α,25OHC promotes oligodendrocyte progenitor cells (OPCs) migration, suggesting a role in myelination. High expression of EBI2 in immune cells and their accumulation in MS lesions supports the idea that the EBI2/7α,25OHC pathway facilitates the migration of inflammatory cells to sites of CNS inflammation in MS. These findings suggest EBI2 signaling is a key regulator of neuroimmune interactions and myelin biology, highlighting its therapeutic potential in demyelinating diseases such as MS.

AIM(S): This study will investigate the molecular and functional effects of increased EBI2 signaling in glial cells including astrocytes, microglia, and OPCs isolated from EBI2 knockout (KO) and WT mice and their role in myelination using organotypic cerebellar slice cultures.

METHOD(S): Cells will be treated with pro-inflammatory cytokines or lipopolysaccharide (LPS) with or without CF3-7α,25OHC to assess EBI2-dependent pathways. Functional outcomes in glial cells such as differentiation, maturation, and inflammatory responses will be evaluated using ELISA, qPCR, Western blot (WB), immunocytochemistry (ICC) along with (re)myelination in organotypic cerebellar slices.

RESULTS: Data collection and analysis are currently ongoing and preliminary findings will be available and presented at the conference.

CONCLUSIONS:

FINANCIAL SUPPORT: The project received funding from the National Science Centre, Poland, grant registration number: 2022/47/D/NZ3/02613 (AR).