Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism

• Published in: PloS one 2012-10, Vol.7 (10), p.e47379-e47379
• Main Authors: Gresle, Melissa M, Alexandrou, Estella, Wu, Qizhu, Egan, Gary, Jokubaitis, Vilija, Ayers, Margaret, Jonas, Anna, Doherty, William, Friedhuber, Anna, Shaw, Gerry, Sendtner, Michael, Emery, Ben, Kilpatrick, Trevor, Butzkueven, Helmut
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Axons; Axons - metabolism; Biology; Brain research; Ciliary neurotrophic factor; Ciliary Neurotrophic Factor - genetics; Ciliary Neurotrophic Factor - metabolism; Clonal deletion; Colonies & territories; Cytokine Receptor gp130 - metabolism; Cytokines; Disease; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - etiology; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - metabolism; Experimental allergic encephalomyelitis; Experiments; Genetic aspects; Glycoprotein gp130; Humans; Inflammation; Injury prevention; Interleukin 6; Kinases; Leukemia; Leukemia inhibitory factor; Leukemia Inhibitory Factor - genetics; Leukemia Inhibitory Factor - metabolism; Lymphocytes T; Magnetic resonance imaging; Medical imaging equipment; Medicine; Mice; Mice, Knockout; Neurobiology; Neurosciences; Oligodendrocytes; Oligodendroglia - metabolism; Optic nerve; Pathology; Priming; Proteins; Rodents; Signal Transduction; Signaling; Spinal cord
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047379

Leukemia 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 2.1±0.14 vs 2.6±0.19; P