LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival

Helmut Butzkueven, Jian Guo Zhang, Merja Soilu-Hanninen, Hubertus Hochrein, Fiona Chionh, Kylie A. Shipham, Ben Emery, Ann M. Turnley, Steven Petratos, Matthias Ernst, Perry F. Bartlett, Trevor J. Kilpatrick

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

Multiple sclerosis (MS) is a disabling inflammatory demyelinating disease of the central nervous system (CNS) that primarily affects young adults. Available therapies can inhibit the inflammatory component of MS but do not suppress progressive clinical disability. An alternative approach would be to inhibit mechanisms that drive the neuropathology of MS, which often includes the death of oligodendrocytes, the cells responsible for myelinating the CNS. Identification of molecular mechanisms that mediate the stress response of oligodendrocytes to optimize their survival would serve this need. This study shows that the neurotrophic cytokine leukemia inhibitory factor (LIF) directly prevents oligodendrocyte death in animal models of MS. We also demonstrate that this therapeutic effect complements endogenous LIF receptor signaling, which already serves to limit oligodendrocyte loss during immune attack. Our results provide a novel approach for the treatment of MS.

Original languageEnglish (US)
Pages (from-to)613-619
Number of pages7
JournalNature Medicine
Volume8
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

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OSM-LIF Receptors
Oligodendroglia
Neurology
Demyelinating Diseases
Multiple Sclerosis
Leukemia Inhibitory Factor
Animals
Cytokines
Central Nervous System
Therapeutic Uses
Young Adult
Cell Death
Animal Models
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Butzkueven, H., Zhang, J. G., Soilu-Hanninen, M., Hochrein, H., Chionh, F., Shipham, K. A., ... Kilpatrick, T. J. (2002). LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Nature Medicine, 8(6), 613-619. https://doi.org/10.1038/nm0602-613

LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. / Butzkueven, Helmut; Zhang, Jian Guo; Soilu-Hanninen, Merja; Hochrein, Hubertus; Chionh, Fiona; Shipham, Kylie A.; Emery, Ben; Turnley, Ann M.; Petratos, Steven; Ernst, Matthias; Bartlett, Perry F.; Kilpatrick, Trevor J.

In: Nature Medicine, Vol. 8, No. 6, 2002, p. 613-619.

Research output: Contribution to journalArticle

Butzkueven, H, Zhang, JG, Soilu-Hanninen, M, Hochrein, H, Chionh, F, Shipham, KA, Emery, B, Turnley, AM, Petratos, S, Ernst, M, Bartlett, PF & Kilpatrick, TJ 2002, 'LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival', Nature Medicine, vol. 8, no. 6, pp. 613-619. https://doi.org/10.1038/nm0602-613
Butzkueven H, Zhang JG, Soilu-Hanninen M, Hochrein H, Chionh F, Shipham KA et al. LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Nature Medicine. 2002;8(6):613-619. https://doi.org/10.1038/nm0602-613
Butzkueven, Helmut ; Zhang, Jian Guo ; Soilu-Hanninen, Merja ; Hochrein, Hubertus ; Chionh, Fiona ; Shipham, Kylie A. ; Emery, Ben ; Turnley, Ann M. ; Petratos, Steven ; Ernst, Matthias ; Bartlett, Perry F. ; Kilpatrick, Trevor J. / LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. In: Nature Medicine. 2002 ; Vol. 8, No. 6. pp. 613-619.
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