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Oncotarget. 2017 Apr 25;8(17):28395-28407. doi: 10.18632/oncotarget.16081.

Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous system demyelination.

Author information

1
Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, China.

Abstract

Interleukin 7 receptor (IL-7R) has been associated with the pathogenesis of multiple sclerosis (MS), though the mechanisms are not clear. Because myelin expression is highly conserved between zebrafish and mammals, zebrafish have become an ideal model for studying demyelination. We used a transgenic (Tg; mbp:nfsB-egfp) zebrafish line in which oligodendrocytes expressed green fluorescent protein (GFP) from the larval stage to adulthood. Exposing adult transgenic zebrafish to metronidazole induced demyelination that resembled the morphological changes associated with the early stages of MS. The metronidazole-induced demyelination was confirmed by magnetic resonance imaging (MRI) for the first time. Microarray analysis revealed down-regulation of IL-7R during demyelination. Targeted knockdown of IL-7R demonstrated that IL-7R is essential for myelination in embryonic and larval zebrafish. Moreover, IL-7R down-regulation induced signaling via the JAK/STAT pathway leading to apoptosis in oligodendrocytes. These findings contribute to our understanding of the role of IL-7R in demyelination, and provide a rationale for the development of IL-7R-based therapies for MS and other demyelinating diseases.

KEYWORDS:

demyelination; interleukin 7 receptor (IL-7R); myelin basic protein; myelination; zebrafish

PMID:
28415697
PMCID:
PMC5438658
DOI:
10.18632/oncotarget.16081
[Indexed for MEDLINE]
Free PMC Article

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