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 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.

• Authors: LiPing Liu, Lisa C Spangler, Briana Prager, Bryan Benson, BingQing Hu, Samuel Shi, Anna Love, CunJin Zhang, Meigen Yu, Anne C Cotleur, Richard M Ransohoff
• Journal: Neurology(R) neuroimmunology & neuroinflammation (Neurol Neuroimmunol Neuroinflamm) Vol. 2 Issue 6 Pg. e174 (Dec 2015) ISSN: 2332-7812 [Print] United States
• PMID: 26668819 (Publication Type: Journal Article)