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

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

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227 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
Pages (from-to)613 - 619
Number of pages7
JournalNature Medicine
Volume8
Issue number6
DOIs
Publication statusPublished - 2002
Externally publishedYes

Cite this

Butzkueven, H., Zhang, J-G., Soilu-Hanninen, M., Hochrein, H., Chionh, F., Shipham, K. A., Emery, B., Turnley, A. M., Petratos, S., Ernst, M. R., Bartlett, P. F., & 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