LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival
Helmut Butzkueven1, Jian-Guo Zhang1, Merja Soilu-Hanninen1, Hubertus Hochrein1, Fiona Chionh1, Kylie A. Shipham1, Ben Emery1, Ann M. Turnley1, Steven Petratos1, Matthias Ernst2, Perry F. Bartlett1
& Trevor J. Kilpatrick1
1
The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Victoria, Australia
2
Ludwig Institute for Cancer Research, The Royal Melbourne Hospital, Victoria, Australia
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.
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