The role of EBI2 for encephalitogenic TH17 cells in EAE and in MS
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Abstract
Epstein-Barr virus-induced gene 2 (EBI2), also termed GPR183, and its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) direct leukocyte migration and localization in secondary lymphoid organs. Using a novel reporter-knockin/knockout (KO) mouse model, we found that IL-23 and IL-1β induced expression of EBI2 in TH17 cells and that its expression by myelin oligodendrocyte glycoprotein (MOG)-specific TH17 cells promotes CNS inflammation in a transfer model of experimental autoimmune encephalomyelitis (EAE). In addition, we found that the enzymes CH25H and CYB7B1, synthesizing 7α,25-OHC from cholesterol, dramatically change expression in spleen and in spinal cord in the course of EAE, being reduced in the spleen and elevated in the CNS upon immunization. Our findings indicate that the distribution of 7 α,25-OHC changes from the periphery to CNS during EAE which fosters transmigration of encephalitogenic TH17 cells into the inflamed CNS via EBI2.