Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination

Leslie Kirby, Jing Jin, Jaime Gonzalez Cardona, Matthew D. Smith, Kyle A. Martin, Jingya Wang, Hayley Strasburger, Leyla Herbst, Maya Alexis, Jodi Karnell, Todd Davidson, Ranjan Dutta, Joan Goverman, Dwight Bergles, Peter A. Calabresi

Research output: Contribution to journalArticle

Abstract

Oligodendrocyte precursor cells (OPCs) are abundant in the adult central nervous system, and have the capacity to regenerate oligodendrocytes and myelin. However, in inflammatory diseases such as multiple sclerosis (MS) remyelination is often incomplete. To investigate how neuroinflammation influences OPCs, we perform in vivo fate-tracing in an inflammatory demyelinating mouse model. Here we report that OPC differentiation is inhibited by both effector T cells and IFNγ overexpression by astrocytes. IFNγ also reduces the absolute number of OPCs and alters remaining OPCs by inducing the immunoproteasome and MHC class I. In vitro, OPCs exposed to IFNγ cross-present antigen to cytotoxic CD8 T cells, resulting in OPC death. In human demyelinated MS brain lesions, but not normal appearing white matter, oligodendroglia exhibit enhanced expression of the immunoproteasome subunit PSMB8. Therefore, OPCs may be co-opted by the immune system in MS to perpetuate the autoimmune response, suggesting that inhibiting immune activation of OPCs may facilitate remyelination.

Original languageEnglish (US)
Article number3887
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination'. Together they form a unique fingerprint.

  • Cite this

    Kirby, L., Jin, J., Cardona, J. G., Smith, M. D., Martin, K. A., Wang, J., Strasburger, H., Herbst, L., Alexis, M., Karnell, J., Davidson, T., Dutta, R., Goverman, J., Bergles, D., & Calabresi, P. A. (2019). Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination. Nature communications, 10(1), [3887]. https://doi.org/10.1038/s41467-019-11638-3