Transfer of myelin-reactive Th17 cells impairs endogenous remyelination in the central nervous system of cuprizone-fed mice

Emily G. Baxi, Joseph DeBruin, Dominique M. Tosi, Inna V. Grishkan, Matthew D. Smith, Leslie A. Kirby, Hayley J. Strasburger, Amanda N. Fairchild, Peter A. Calabresi, Anne R. Gocke

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Multiple sclerosis (MS) is a demyelinating disease of the CNS characterized by inflammation and neurodegeneration. Animal models that enable the study of remyelination in the context of ongoing inflammation are greatly needed for the development of novel therapies that target the pathological inhibitory cues inherent to theMSplaque microenvironment.Wereport the development of an innovative animal model combining cuprizone-mediated demyelination with transfer of myelin-reactive CD4+ T cells. Characterization of this model reveals both Th1 and Th17 CD4+ T cells infiltrate the CNS of cuprizone-fed mice, with infiltration of Th17 cells being more efficient. Infiltration correlates with impaired spontaneous remyelination as evidenced by myelin protein expression, immunostaining, and ultrastructural analysis. Electron microscopic analysis further reveals that demyelinated axons are preserved but reduced in caliber. Examination of the immune response contributing to impaired remyelination highlights a role for peripheral monocytes with an M1 phenotype. This study demonstrates the development of a novel animal model that recapitulates elements of the microenvironment of the MSplaque and reveals an important role forTcells and peripheral monocytes in impairing endogenous remyelination in vivo. This model could be useful for testing putative MS therapies designed to enhance remyelination in the setting of active inflammation, and may also facilitate modeling the pathophysiology of denuded axons, which has been a challenge in rodents because they typically remyelinate very quickly.

Original languageEnglish (US)
Pages (from-to)8626-8639
Number of pages14
JournalJournal of Neuroscience
Issue number22
StatePublished - Jun 3 2015


  • Axons
  • Cuprizone
  • Demyelination
  • Inflammation
  • Multiple sclerosis
  • Oligodendrocyte precursor cells

ASJC Scopus subject areas

  • Neuroscience(all)


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