| Description |
Cxcr2 is a chemokine receptor expressed on oligodendroglia that has been implicated in the pathogenesis of neuroinflammatory demyelinating diseases as well as enhancing the migration, proliferation, and myelin production by oligodendroglia. Using an inducible proteolipid protein (Plp) promoter-driven Cre-loxP recombination system, we were able to assess how timed ablation of Cxcr2 in oligodendroglia affected disease following intracranial (i.c.) infection with the neurotropic John Howard Müeller (JHM) strain of mouse hepatitis virus (JHMV). Generation of Plp-Cre-ER(T) :: Cxcr2fl/fl transgenic mice (termed Cxcr2-CKO mice) allows for Cxcr2 to be silenced in oligodendrocytes in adult mice following treatment with tamoxifen. Ablation of oligodendroglia Cxcr2 did not influence clinical severity in response to i.c. infection with JHMV. Infiltration of activated T cells or myeloid cells into the central nervous system (CNS) was not affected nor was the ability to control viral infection. In addition, the severity of demyelination was similar between tamoxifen-treated mice compared to vehicletreated controls. Notably, deletion of Cxcr2 resulted in increased myelin basic protein (MBP) staining and remyelination as assessed by g-ratio calculation when compared to vehicle-treated control mice. Collectively, our findings argue that Cxcr2 signaling in oligodendroglia is dispensable with regards to contributing to neuroinflammation, but its deletion enhances remyelination in a pre-clinical model of the human demyelinating disease multiple sclerosis (MS). |
