Evidence map›Paper›PMID 34452924›Full record

ArticleScience immunology2021

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

Open access · greenAbstract read
In one paragraph

Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Genetic or therapeutic disruption of the Reelin/Apoer2 signaling pathway improves inflammatory arthritis outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Apolipoprotein E in Cardiometabolic and Neurological Health and Diseases.International journal of molecular sciences · 2022
    Review
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Laurent CalvierDepartment of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA. calvier.laurent@gmail.com joachim.herz@utsouthwestern.edu.ORCID 0000-0001-6437-2119
Navid ManouchehriDepartment of Neurology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-5773-2622
Anastasia SacharidouCenter for Pulmonary and Vascular Biology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-8474-4028
Chieko MineoCenter for Pulmonary and Vascular Biology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-4978-6177
Philip W ShaulCenter for Pulmonary and Vascular Biology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1157-4002
David Y HuiDepartment of Pathology, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0001-7333-2151
Maria Z KounnasReelin Therapeutics Inc., La Jolla, CA, USA.
Olaf StüveDepartment of Neurology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-0469-6872
Joachim HerzDepartment of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA. calvier.laurent@gmail.com joachim.herz@utsouthwestern.edu.ORCID 0000-0002-8506-3400
Southwestern Medical Center · USRodin Therapeutics (United States) · US

Funding

TRAINING PROGRAM IN LUNG BIOLOGY AND DISEASET32HL098040 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI SHAUL, PHILIP W, TERADA, LANCE S · 2009 to 2024
$4.6M
Validation of Modulators of PGRN as Novel Therapeutics for Frontotemporal DementiR01NS108115 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI HAGGARTY, STEPHEN J, HERZ, JOACHIM J · 2018 to 2022
$4.0M
Metabolism of the VLDL receptor and ApoE receptor 2R37HL063762 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2010 to 2019
$4.0M
METABOLISM OF THE VLDL RECEPTOR AND APOE RECEPTOR 2R01HL063762 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2000 to 2009
$3.1M
ApoE receptor-2 in vascular disease progression and regressionR01HL147403 · NHLBI · UNIVERSITY OF CINCINNATI · PI HUI, DAVID YIU-KWAN · 2019 to 2022
$3.0M
Unraveling ApoE4 Promotion of Cardiometabolic DiseaseR01HL144969 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI SHAUL, PHILIP W · 2020 to 2023
$2.6M
Physiology and Pathophysiology of Apolipoprotein E receptor-2 splicing in Alzheimer's diseaseRF1AG053391 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2016 to 2020
$2.4M
Molecular Basis of Synaptic Suppression by ApoER01NS093382 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2016 to 2020
$2.0M
Molecular Basis of Pregnancy Complications in the Antiphospholipid SyndromeR01HD094395 · NICHD · UT SOUTHWESTERN MEDICAL CENTER · PI MINEO, CHIEKO · 2018 to 2022
$1.8M
Endothelial Basis of Obesity-induced Insulin ResistanceR01DK110127 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI MINEO, CHIEKO · 2016 to 2019
$1.8M
Dichotomous Role of Endothelial SR-BI in AtherosclerosisR01HL131597 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI SHAUL, PHILIP W · 2017 to 2020
$1.6M
Mitochondrial mechanisms underlying alveolar-capillary barrier regulationK08HL148403 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HOUGH, REBECCA FRANCES · 2020 to 2024
$827k
BLRD VA I01 BX005664NHLBI NIH HHS K08 HL148403NHLBI NIH HHS R01 HL063762NHLBI NIH HHS R01 HL131597NHLBI NIH HHS R01 HL144969NHLBI NIH HHS R01 HL147403NHLBI NIH HHS R37 HL063762NHLBI NIH HHS T32 HL098040NIA NIH HHS RF1 AG053391NICHD NIH HHS R01 HD094395NIDDK NIH HHS R01 DK110127NINDS NIH HHS R01 NS093382NINDS NIH HHS R01 NS108115
6 · The paper itself

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.

Indexed as

AnimalsCell AdhesionEncephalomyelitis, Autoimmune, ExperimentalEndothelium, VascularLDL-Receptor Related ProteinsMaleMiceMice, KnockoutMonocytesLDL-Receptor Related Proteinslow density lipoprotein receptor-related protein 8

Identifiers

PMID34452924
PMCPMC8627794
OpenAlexW3195923607

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.