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

Background: Residual CXCR2 expression on CNS cells in Cxcr2 +/− → Cxcr2 −/− chimeric animals slowed remyelination after both experimental autoimmune encephalomyelitis and cuprizone-induced demyelination. Methods: We generated Cxcr2 fl/− :PLPCre-ER(T) mice enabling an inducible, conditional deletion of Cxcr2 on oligodendrocyte lineage cells of the CNS. Cxcr2 fl/− :PLPCre-ER(T) mice were evaluated in 2 demyelination/remyelination models: cuprizone-feeding and in vitro lysophosphatidylcholine (LPC) treatment of cerebellar slice cultures. Results: Cxcr2 fl/− :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.