Interferon-γ inhibits central nervous system myelination through both STAT1-dependent and STAT1-independent pathways.

Journal of Neuroscience Research
Wensheng Lin, Yifeng Lin

Abstract

The immune cytokine interferon-gamma (IFN-gamma) plays a crucial role in immune-mediated demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Our previous studies have shown that enforced expression of IFN-gamma in the central nervous system (CNS) inhibits developmental myelination or remyelination in EAE demyelinated lesions. Although many of the cellular actions of IFN-gamma result from its activation of the signal transducer and activator of transcription 1 (STAT1) pathway, recent studies have shown that STAT1-independent pathways regulate some facets of IFN-gamma biology. In this study, we dissected the role ofSTAT1-dependent and STAT1-independent pathways in IFN-gamma-induced hypomyelination using a genetic approach. We found that the induction of STAT1-dependent, IFN-gamma-responsive genes in response to this cytokine was abolished in the CNS of STAT1 null mice. Moreover, STAT1 deletion diminished oligodendrocyte loss, reduction of myelinated axons, and the inflammatory response in the CNS of transgenic mice that ectopically expressed IFN-gamma in the CNS. Nevertheless, IFN-gamma-induced reduction of myelin sheath thickness in the CNS of these mice was not altered by STAT1...Continue Reading

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Citations

Apr 5, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wensheng LinBrian Popko
Aug 29, 2013·Immunology·Laura PeferoenSandra Amor
Aug 19, 2015·Frontiers in Neuroscience·Sarrabeth Stone, Wensheng Lin
Jan 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lauren A O'DonnellGlenn F Rall
Jul 21, 2015·Journal of Neurochemistry·Lauren A O'DonnellGlenn F Rall
Jun 28, 2017·The Journal of Biological Chemistry·Daniel S GreenJulio C Valencia
Oct 23, 2019·Neural Regeneration Research·Wensheng Lin, Sarrabeth Stone
Jul 22, 2018·BioMed Research International·Larisa Montalvo-MartínezAlberto Camacho

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