Low-density lipoprotein receptor deficiency attenuates neuroinflammation through the induction of apolipoprotein E

Jo Mailleux, Silke Timmermans, Katherine Nelissen, Jasmine Vanmol, Tim Vanmierlo, Jack van Horssen, Jeroen F.J. Bogie, Jerome J.A. Hendriks*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: We aimed to determine the role of the low-density lipoprotein receptor (LDLr) in neuroinflammation by inducing experimental autoimmune encephalomyelitis (EAE) in ldlr knock out mice. Methods: MOG35-55 induced EAE in male and female ldlr-/- mice was assessed clinically and histopathologically. Expression of inflammatory mediators and apolipoprotein E (apoE) was investigated by qPCR. Changes in protein levels of apoE and tumor necrosis factor alpha (TNFα) were validated by western blot and ELISA, respectively. Results: Ldlr-/--attenuated EAE disease severity in female, but not in male, EAE mice marked by a reduced proinflammatory cytokine production in the central nervous system of female ldlr-/- mice. Macrophages from female ldlr-/- mice showed a similar decrease in proinflammatory mediators, an impaired capacity to phagocytose myelin and enhanced secretion of the anti-inflammatory apoE. Interestingly, apoE/ldlr double knock out abrogated the beneficial effect of ldlr depletion in EAE. Conclusion: Collectively, we show that ldlr-/- reduces EAE disease severity in female but not in male EAE mice, and that this can be explained by increased levels of apoE in female ldlr-/- mice. Although the reason for the observed sexual dimorphism remains unclear, our findings show that LDLr and associated apoE levels are involved in neuroinflammatory processes.

Original languageEnglish
Article number1701
JournalFrontiers in Immunology
Volume8
Issue numberNOV
DOIs
Publication statusPublished - 30 Nov 2017

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