Evidence map›Paper›PMID 40071147›Full record

ArticleiScience2025

IQGAP2 regulates blood-brain barrier immune dynamics.

Ketaki A Katdare, Andrew Kjar, Natasha M O'Brown, Emma H Neal, Alexander G Sorets, Alena Shostak, Wilber Romero-Fernandez, Alexander J Kwiatkowski, Kate Mlouk, Hyosung Kim and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Ketaki A KatdareVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Andrew KjarDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Natasha M O'BrownDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Emma H NealDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Alexander G SoretsDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Alena ShostakDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Wilber Romero-FernandezDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Alexander J KwiatkowskiDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Kate MloukDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Hyosung KimDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Rebecca P CowellDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Katrina R SchwensenDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Cristian O Carvajal TapiaDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Guste VenslovaiteDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Kensley B HornerDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
John T WilsonDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Matthew S SchragVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Sean G MegasonDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Ethan S LippmannVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.

Funding

Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey L Neul · 2020 to 2026
$10.3M
Elucidating Novel Human Blood-Brain Barrier ComponentsR21NS106510 · NINDS · VANDERBILT UNIVERSITY · PI LIPPMANN, ETHAN · 2018 to 2019
$432k
NICHD NIH HHS P50 HD103537NINDS NIH HHS R21 NS106510
6 · The paper itself

Abstract

Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase-activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions. Using single-cell RNA sequencing and immunohistology, we further show that BECs from mice lacking Iqgap2 exhibit a profound inflammatory signature, including extensive upregulation of adhesion receptors and antigen-processing machinery. Human tissue analyses also reveal that Alzheimer's disease is associated with reduced hippocampal IQGAP2. Overall, our results implicate IQGAP2 as an essential regulator of BBB immune privilege and immune cell entry into the CNS.

Indexed as

immunologyneuroscience

Identifiers

PMID40071147
PMCPMC11894336

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.