Interferon-gamma, oligodendrocyte injury and inflammatory demyelination

David Liebenson, Roumen Balabanov*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Interferon-gamma (IFN-γ) is a pleiotropic inflammatory cytokine produced by T cells and natural killer cells. It is critically involved in the pathogenesis of the human demyelinating disease multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE). These diseases are mediated by activated self-reactive T cells, which target the central nervous system (CNS) oligodendrocytes and their myelin sheaths. In addition to its immunoregulatory properties, IFN-γ exerts a direct biological effect on CNS cells, providing, thereby, a link between CNS inflammation and cell injury. In this review, we discuss the role of IFN-γ in MS and EAE, as well as its involvement in the processes of oligodendrocyte injury and inflammatory demyelination. We summarize the molecular mechanisms of IFN-γ-induced oligodendrocyte injury and analyze the various experimental models that have been used for their elucidation. Finally, we discuss the disease-promoting role of IFN-γ's IRF-1/Caspase 1 signaling in MS and EAE, and draw attention to the potential therapeutic significance of its suppression. In conclusion, studying IFN-γ - oligodendrocyte interactions is likely to provide new perspective on the pathogenesis of MS.

Original languageEnglish (US)
Title of host publicationInterferons
Subtitle of host publicationCharacterization, Mechanism of Action and Clinical Applications
PublisherNova Science Publishers, Inc.
Pages67-82
Number of pages16
ISBN (Print)9781620812983
StatePublished - Sep 1 2012

Keywords

  • Caspase 1
  • Cell signaling
  • Demyelination
  • Experimental autoimmune encephalomyelitis
  • IRF-1
  • Inflammation
  • Interferon-gamma
  • Multiple sclerosis
  • Oligodendrocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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