Low-Density Lipoprotein Receptor Deficiency Attenuates Neuroinflammation through the Induction of Apolipoprotein E

Jo Mailleux1, Silke Timmermans1, Katherine Nelissen1

  • 1Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.

Frontiers in Immunology
|December 26, 2017
PubMed
Abstract

Insights

Low-density lipoprotein receptor (LDLr) deficiency attenuated experimental autoimmune encephalomyelitis (EAE) in female mice by increasing apolipoprotein E (apoE). This highlights LDLr

Area of Science:

  • Neuroimmunology
  • Lipid Metabolism
  • Autoimmune Diseases

Background:

  • Neuroinflammation is a key component of multiple sclerosis and other neurological disorders.
  • The low-density lipoprotein receptor (LDLr) plays a role in cholesterol homeostasis.
  • The involvement of LDLr in neuroinflammatory processes remains incompletely understood.

Purpose of the Study:

  • To investigate the role of LDLr in neuroinflammation using a mouse model of experimental autoimmune encephalomyelitis (EAE).
  • To determine the impact of LDLr deficiency on EAE disease severity and underlying inflammatory mechanisms.

Main Methods:

  • Induction of MOG35-55 EAE in LDLr knockout (ldlr-/-) mice (male and female).
  • Clinical and histopathological assessment of EAE.
  • Quantitative PCR (qPCR) for inflammatory mediators and apolipoprotein E (apoE).
  • Western blot and ELISA for apoE and TNFα protein levels.

Main Results:

  • LDLr deficiency attenuated EAE severity in female mice, but not in males.
  • Female ldlr-/- mice exhibited reduced central nervous system proinflammatory cytokine production.
  • Macrophages from female ldlr-/- mice showed decreased proinflammatory mediators, impaired myelin phagocytosis, and enhanced apoE secretion.
  • ApoE/LDLr double knockout abrogated the protective effect of LDLr depletion in EAE.

Conclusions:

  • LDLr deficiency reduces EAE severity in female mice, linked to increased apoE levels.
  • The observed sexual dimorphism in EAE response warrants further investigation.
  • LDLr and apoE are implicated in modulating neuroinflammatory processes.

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