Suppressor of cytokine signaling 1 expression protects oligodendrocytes from the deleterious effects of interferon-γ

Roumen Balabanov, Krystal Strand, April Kemper, Yeon Lee Ji, Brian Popko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Interferon-γ (IFN-γ) is a pleiotropic cytokine produced by T cells and natural killer cells that has been implicated as a deleterious factor in the immune-mediated demyelinating disorder multiple sclerosis. In vitro, purified developing and mature oligodendrocytes have been shown to die in the presence of IFN-γ by apoptosis and necrosis, respectively. Moreover, transgenic expression of IFN-γ in the CNS of mice during development results in tremor, hypomyelination, and oligodendrocyte cell loss, and IFN-γ expression in adult animals after demyelinating insults inhibits remyelination. To examine the molecular mechanisms of IFN-γ-induced oligodendrocyte injury, we generated a transgenic mouse line [PLP/SOCS1 (proteolipid protein/suppressor of cytokine signaling 1)] that exhibits diminished oligodendrocyte responsiveness to IFN-γ attributable to the targeted expression of SOCS1 in these cells. We demonstrate that oligodendrocytes in the PLP/SOCS1 transgenic mice are protected against the injurious effect of IFN-γ. Our data indicate that IFN-γ exerts a direct deleterious effect on developing oligodendrocytes. The capacity of SOCS1 to inhibit the effects of IFN-γ suggests a therapeutic approach toward protection of myelinating oligodendrocytes against the harmful effects of inflammation.

Original languageEnglish (US)
Pages (from-to)5143-5152
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number19
DOIs
StatePublished - 2006

Keywords

  • Interferon-γ
  • Myelin
  • Oligodendrocytes
  • SOCS1
  • Stat1
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

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