Evidence map›Paper›PMID 32801146›Full record

ArticleScience translational medicine2020

Reelin depletion protects against autoimmune encephalomyelitis by decreasing vascular adhesion of leukocytes.

Laurent Calvier, Guillaume Demuth, Navid Manouchehri, Connie Wong, Anastasia Sacharidou, Chieko Mineo, Philip W Shaul, Nancy L Monson, Maria Z Kounnas, Olaf Stüve and 1 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. 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
  7. Article
  8. Leukocyte-lymphatic intersections during cardiac inflammation.Journal of molecular and cellular cardiology · 2025
    Review
  9. The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024
    Review
  10. Article
  11. Unraveling the Impact ofLife (Basel, Switzerland) · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Editorial: New Advances in Cardiorenal Syndrome.Frontiers in cardiovascular medicine · 2022
    Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 1 country.

Laurent CalvierDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. calvier.laurent@gmail.com joachim.herz@utsouthwestern.edu.ORCID 0000-0001-6437-2119
Guillaume DemuthDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Navid ManouchehriDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Connie WongDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-6452-7966
Anastasia SacharidouCenter for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-8474-4028
Chieko MineoCenter for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-4978-6177
Philip W ShaulCenter for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Nancy L MonsonDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Maria Z KounnasReelin Therapeutics Inc. La Jolla, CA 92037, USA.
Olaf StüveDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Joachim HerzDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. calvier.laurent@gmail.com joachim.herz@utsouthwestern.edu.ORCID 0000-0002-8506-3400
The University of Texas Southwestern Medical Center · USRodin Therapeutics (United States) · USVA North Texas Health Care System · 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
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
Dichotomous Role of Endothelial SR-BI in AtherosclerosisR01HL131597 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI SHAUL, PHILIP W · 2017 to 2020
$1.6M
Discovery of Novel Interventions of the Antiphospholipid SyndromeR01HL109604 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI MINEO, CHIEKO · 2011 to 2014
$1.6M
NHLBI NIH HHS R01 HL109604NHLBI NIH HHS R01 HL131597NHLBI NIH HHS R01 HL144969NHLBI NIH HHS R37 HL063762NHLBI NIH HHS T32 HL098040NIA NIH HHS RF1 AG053391NICHD NIH HHS R01 HD094395NINDS NIH HHS R01 NS093382NINDS NIH HHS R01 NS108115
6 · The paper itself

Abstract

Neuroinflammation as a result of immune cell recruitment into the central nervous system (CNS) is a key pathogenic mechanism of multiple sclerosis (MS). However, current anti-inflammatory interventions depleting immune cells or directly targeting their trafficking into the CNS can have serious side effects, highlighting a need for better immunomodulatory strategies. We detected increased Reelin concentrations in the serum of patients with MS, resulting in increased endothelial permeability to leukocytes through increased nuclear factor κB-mediated expression of vascular adhesion molecules. We thus investigated the prophylactic and therapeutic potential of Reelin immunodepletion in experimental autoimmune encephalomyelitis (EAE) and further validated the results in Reelin knockout mice. Removal of plasma Reelin by either approach protected against neuroinflammation and largely abolished the neurological consequences by reducing endothelial permeability and immune cell accumulation in the CNS. Our findings suggest Reelin depletion as a therapeutic approach with an inherent good safety margin for the treatment of MS and other diseases where leukocyte extravasation is a major driver of pathogenicity.

Indexed as

EncephalomyelitisEncephalomyelitis, Autoimmune, ExperimentalMultiple SclerosisAnimalsCentral Nervous SystemHumansLeukocytesMiceMice, Inbred C57BLReelin ProteinReelin Protein

Identifiers

PMID32801146
PMCPMC7860587
OpenAlexW3048848956

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.