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

Melissa M Gresle; Estella Alexandrou; Qi-Zhu Wu; Gary Francis Egan; Vilija Jokubaitis; Margaret Ayers; Anna Jonas; William Doherty; Anna Friedhuber; Gerry Shaw; Michael Sendtner; Ben Emery; Trevor Kilpatrick; Helmut Butzkueven

doi:10.1371/journal.pone.0047379

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

Melissa M Gresle, Estella Alexandrou, Qi-Zhu Wu, Gary Francis Egan, Vilija Jokubaitis, Margaret Ayers, Anna Jonas, William Doherty, Anna Friedhuber, Gerry Shaw, Michael Sendtner, Ben Emery, Trevor Kilpatrick, Helmut Butzkueven

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Abstract

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.

Original language	English
Article number	e47379
Number of pages	12
Journal	PLoS ONE
Volume	7
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0047379
Publication status	Published - 2012

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Gresle, M. M., Alexandrou, E., Wu, Q.-Z., Egan, G. F., Jokubaitis, V., Ayers, M., Jonas, A., Doherty, W., Friedhuber, A., Shaw, G., Sendtner, M., Emery, B., Kilpatrick, T., & Butzkueven, H. (2012). Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism. PLoS ONE, 7(10), Article e47379. https://doi.org/10.1371/journal.pone.0047379

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title = "Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism",

abstract = "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.",

author = "Gresle, {Melissa M} and Estella Alexandrou and Qi-Zhu Wu and Egan, {Gary Francis} and Vilija Jokubaitis and Margaret Ayers and Anna Jonas and William Doherty and Anna Friedhuber and Gerry Shaw and Michael Sendtner and Ben Emery and Trevor Kilpatrick and Helmut Butzkueven",

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Gresle, MM, Alexandrou, E, Wu, Q-Z, Egan, GF , Jokubaitis, V, Ayers, M, Jonas, A, Doherty, W, Friedhuber, A, Shaw, G, Sendtner, M, Emery, B, Kilpatrick, T & Butzkueven, H 2012, 'Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism', PLoS ONE, vol. 7, no. 10, e47379. https://doi.org/10.1371/journal.pone.0047379

TY - JOUR

T1 - Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism

AU - Gresle, Melissa M

AU - Alexandrou, Estella

AU - Wu, Qi-Zhu

AU - Egan, Gary Francis

AU - Jokubaitis, Vilija

AU - Ayers, Margaret

AU - Jonas, Anna

AU - Doherty, William

AU - Friedhuber, Anna

AU - Shaw, Gerry

AU - Sendtner, Michael

AU - Emery, Ben

AU - Kilpatrick, Trevor

AU - Butzkueven, Helmut

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

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DO - 10.1371/journal.pone.0047379

M3 - Article

SN - 1932-6203

VL - 7

JO - PLoS ONE

JF - PLoS ONE

IS - 10

M1 - e47379

ER -

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

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