Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells

Zizhen Kang; Chenhui Wang; Jarod Zepp; Ling Wu; Kevin Sun; Junjie Zhao; Unni Chandrasekharan; Paul E DiCorleto; Bruce D Trapp; Richard M Ransohoff; Xiaoxia Li

doi:10.1038/nn.3505

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Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells

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Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells

Zizhen Kang, Chenhui Wang, Jarod Zepp, Ling Wu, Kevin Sun, Junjie Zhao, Unni Chandrasekharan, Paul E DiCorleto, Bruce D Trapp, Richard M Ransohoff, …

Nature neuroscience, Vol.16(10), pp.1401-1408

10/2013

DOI: 10.1038/nn.3505

PMCID: PMC4106025

PMID: 23995070

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https://www.ncbi.nlm.nih.gov/pmc/articles/4106025View

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Abstract

Interleukin 17(IL-17) is a signature cytokine of Th17 cells. We previously reported that deletion of NF-κ B activator 1(Act1), the key transducer of IL-17R signaling, from the neuroectodermal lineage in mice (neurons, oligodendrocytes, astrocytes)results in attenuated severity of experimental autoimmune encephalomyelitis (EAE). Here we examined the cellular basis of this observation. EAE disease course was unaffected by deleting Act1 from neurons or mature oligodendrocytes and Act1 deletion from astrocytes only modestly affected disease course. Deletion of Act1 from NG2 + glia resulted in markedly reduced EAE severity. Furthermore, IL-17 induced characteristic inflammatory mediator expression in NG2 + glial cells. Additionally, IL-17 also exhibited strong inhibitory effects on the maturation of oligodendrocyte lineage cells in vitro and reduced their survival. These data identify NG2 + glia as the major CNS cellular target of IL-17 in EAE. The sensitivity of oligodendrocyte lineage cells to IL-17-mediated toxicity further suggests a direct link between inflammation and neurodegeneration in multiple sclerosis (MS).

Details

Title: Subtitle: Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells
Creators: Zizhen Kang - Shanghai Jiao Tong University
Chenhui Wang - Cleveland Clinic
Jarod Zepp - Cleveland Clinic
Ling Wu - Cleveland Clinic
Kevin Sun - Cleveland Clinic
Junjie Zhao - Cleveland Clinic
Unni Chandrasekharan - Cleveland Clinic
Paul E DiCorleto - Cleveland Clinic
Bruce D Trapp - Cleveland Clinic
Richard M Ransohoff - Cleveland Clinic
Xiaoxia Li - Cleveland Clinic
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.16(10), pp.1401-1408
DOI: 10.1038/nn.3505
PMID: 23995070
PMCID: PMC4106025
NLM abbreviation: Nat Neurosci
ISSN: 1097-6256
eISSN: 1546-1726
Language: English
Date published: 10/2013
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984201120702771

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