Spatiotemporal ablation of CXCR2 on oligodendrocyte lineage cells: Role in myelin repair

Abstract

Background: Residual CXCR2 expression on CNS cells in Cxcr2+/-→Cxcr2-/- chimeric animals slowed remyelination after both experimental autoimmune encephalomyelitis and cuprizoneinduced demyelination. Methods: We generated Cxcr2fl/-:PLPCre-ER(T) mice enabling an inducible, conditional deletion of Cxcr2 on oligodendrocyte lineage cells of the CNS. Cxcr2fl/-:PLPCre-ER(T) mice were evaluated in 2 demyelination/remyelination models: cuprizone-feeding and in vitro lysophosphatidylcholine (LPC) treatment of cerebellar slice cultures. Results: Cxcr2fl/-:PLPCre-ER(T)+ (termed Cxcr2-cKO) mice showed better myelin repair 4 days after LPC-induced demyelination of cerebellar slice cultures. Cxcr2-cKOs also displayed enhanced hippocampal remyelination after a 2-week recovery from 6-week cuprizone feeding. Conclusion: Using 2 independent demyelination/remyelination models, our data document enhanced myelin repair in Cxcr2-cKO mice, consistent with the data obtained from radiation chimerism studies of germline CXCR2. Further experiments are appropriate to explore how CXCR2 function in the oligodendrocyte lineage accelerates myelin repair.