AUTHOR=Mailleux Jo , Timmermans Silke , Nelissen Katherine , Vanmol Jasmine , Vanmierlo Tim , van Horssen Jack , Bogie Jeroen F. J. , Hendriks Jerome J. A.
TITLE=Low-Density Lipoprotein Receptor Deficiency Attenuates Neuroinflammation through the Induction of Apolipoprotein E
JOURNAL=Frontiers in Immunology
VOLUME=8
YEAR=2017
URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01701
DOI=10.3389/fimmu.2017.01701
ISSN=1664-3224
ABSTRACT=ObjectiveWe 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.
MethodsMOG35–55 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.
ResultsLdlr−/−-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.
ConclusionCollectively, 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.