Apolipoprotein E receptor 2 deficiency decreases endothelial adhesion of monocytes and protects against autoimmune encephalomyelitis

Laurent Calvier, Navid Manouchehri, Anastasia Sacharidou, Chieko Mineo, Philip W. Shaul, David Y. Hui, Maria Z. Kounnas, Olaf Stüve, Joachim Herz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Under normal conditions, the blood-brain barrier effectively regulates the passage of immune cells into the central nervous system (CNS). However, under pathological conditions such as multiple sclerosis (MS), leukocytes, especially monocytes, infiltrate the CNS where they promote inflammatory demyelination, resulting in paralysis. Therapies targeting the immune cells directly and preventing leukocyte infiltration exist for MS but may compromise the immune system. Here, we explore how apolipoprotein E receptor 2 (ApoER2) regulates vascular adhesion and infiltration of monocytes during inflammation. We induced experimental autoimmune encephalitis in ApoER2 knockout mice and in mice carrying a loss-of-function mutation in the ApoER2 cytoplasmic domain. In both models, paralysis and neuroinflammation were largely abolished as a result of greatly diminished monocyte adherence due to reduced expression of adhesion molecules on the endothelial surface. Our findings expand our mechanistic understanding of the vascular barrier, the regulation of inflammation and vascular permeability, and the therapeutic potential of ApoER2-targeted therapies.

Original languageEnglish (US)
Article numberabd0931
JournalScience Immunology
Volume6
Issue number62
DOIs
StatePublished - Aug 19 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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