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dc.contributor.authorGresle, Melissa M
dc.contributor.authorAlexandrou, Estella
dc.contributor.authorWu, Qizhu
dc.contributor.authorEgan, Gary
dc.contributor.authorJokubaitis, Vilija
dc.contributor.authorAyers, Margaret
dc.contributor.authorJonas, Anna
dc.contributor.authorDoherty, William
dc.contributor.authorFriedhuber, Anna
dc.contributor.authorShaw, Gerry
dc.contributor.authorSendtner, Michael
dc.contributor.authorEmery, Ben
dc.contributor.authorKilpatrick, Trevor
dc.contributor.authorButzkueven, Helmut
dc.date.accessioned2018-01-12T01:02:13Z
dc.date.available2018-01-12T01:02:13Z
dc.date.issued2012
dc.date.modified2013-09-17T23:28:20Z
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0047379
dc.identifier.urihttp://hdl.handle.net/10072/53198
dc.description.abstractLeukemia inhibitory factor (LIF) and Ciliary Neurotrophic factor (CNTF) are members of the interleukin-6 family of cytokines, defined by use of the gp130 molecule as an obligate receptor. In the murine experimental autoimmune encephalomyelitis (EAE) model, antagonism of LIF and genetic deletion of CNTF worsen disease. The potential mechanism of action of these cytokines in EAE is complex, as gp130 is expressed by all neural cells, and could involve immuno-modulation, reduction of oligodendrocyte injury, neuronal protection, or a combination of these actions. In this study we aim to investigate whether the beneficial effects of CNTF/LIF signalling in EAE are associated with axonal protection; and whether this requires signalling through oligodendrocytes. We induced MOG35-55 EAE in CNTF, LIF and double knockout mice. On a CNTF null background, LIF knockout was associated with increased EAE severity (EAE grade 2.1ᰮ14 vs 2.6ᰮ19; P<0.05). These mice also showed increased axonal damage relative to LIF heterozygous mice, as indicated by decreased optic nerve parallel diffusivity on MRI (1540Ჰ7 孲-/s vs 1310ᱷ5 孲-/s; P<0.05), and optic nerve (-12.5%) and spinal cord (-16%) axon densities; and increased serum neurofilament-H levels (2.5 fold increase). No differences in inflammatory cell numbers or peripheral auto-immune T-cell priming were evident. Oligodendrocyte-targeted gp130 knockout mice showed that disruption of CNTF/LIF signalling in these cells has no effect on acute EAE severity. These studies demonstrate that endogenous CNTF and LIF act centrally to protect axons from acute inflammatory destruction via an oligodendrocyte-independent mechanism.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome47379-1
dc.relation.ispartofpagetoe47379-12
dc.relation.ispartofissue10
dc.relation.ispartofjournalPloS One
dc.relation.ispartofvolume7
dc.rights.retentionY
dc.subject.fieldofresearchMedical and Health Sciences not elsewhere classified
dc.subject.fieldofresearchcode119999
dc.titleLeukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2012 Gresle et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.date.issued2012
gro.hasfulltextFull Text
gro.griffith.authorButzkueven, Helmut


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