Evidence map›Paper›PMID 36180898›Full record

ArticleActa neuropathologica communications2022

Ex vivo expanded human regulatory T cells modify neuroinflammation in a preclinical model of Alzheimer's disease.

Alireza Faridar, Matthew Vasquez, Aaron D Thome, Zheng Yin, Hui Xuan, Jing Hong Wang, Shixiang Wen, Xuping Li, Jason R Thonhoff, Weihua Zhao and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 3 pooled it
4.1field-weighted citation impact, top 5% 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

46 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 citations in OpenAlex.

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  14. Tuft Cells in the Gut Limit Cognitive Disorders by Regulating Gut Homeostasis.Cellular and molecular gastroenterology and hepatology · 2026
    Article
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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

15 authors at 2 institutions in 1 country.

Alireza FaridarStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Matthew VasquezSystems Medicine and Bioengineering Department, Houston Methodist Cancer Center, Houston, TX, USA.
Aaron D ThomeStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Zheng YinSystems Medicine and Bioengineering Department, Houston Methodist Cancer Center, Houston, TX, USA.
Hui XuanStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Jing Hong WangStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Shixiang WenStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Xuping LiT. T. and W. F. Chao Center for BRAIN, Houston Methodist Hospital, Houston, TX, USA.
Jason R ThonhoffStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Weihua ZhaoStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Hong ZhaoSystems Medicine and Bioengineering Department, Houston Methodist Cancer Center, Houston, TX, USA.
David R BeersStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Stephen T C WongSystems Medicine and Bioengineering Department, Houston Methodist Cancer Center, Houston, TX, USA.
Joseph C MasdeuStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA.
Stanley H AppelStanley H. Appel Department of Neurology, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX, 77030, USA. sappel@houstonmethodist.org.ORCID 0000-0003-2747-6298
Houston Methodist · USMethodist Hospital · US

Funding

Systematic identification of astrocyte-tumor crosstalk regulating brain metastatic tumorsR01CA238727 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WONG, STEPHEN TC, ZHAO, HONG · 2020 to 2024
$2.6M
NCI NIH HHS R01 CA238727
6 · The paper itself

Abstract

backgroundRegulatory T cells (Tregs) play a neuroprotective role by suppressing microglia and macrophage-mediated inflammation and modulating adaptive immune reactions. We previously documented that Treg immunomodulatory mechanisms are compromised in Alzheimer's disease (AD). Ex vivo expansion of Tregs restores and amplifies their immunosuppressive functions in vitro. A key question is whether adoptive transfer of ex vivo expanded human Tregs can suppress neuroinflammation and amyloid pathology in a preclinical mouse model.

methodsAn immunodeficient mouse model of AD was generated by backcrossing the 5xFAD onto Rag2 knockout mice (5xFAD-Rag2KO). Human Tregs were expanded ex vivo for 24 days and administered to 5xFAD-Rag2KO. Changes in amyloid burden, microglia characteristics and reactive astrocytes were evaluated using ELISA and confocal microscopy. NanoString Mouse AD multiplex gene expression analysis was applied to explore the impact of ex vivo expanded Tregs on the neuroinflammation transcriptome.

resultsElimination of mature B and T lymphocytes and natural killer cells in 5xFAD-Rag2KO mice was associated with upregulation of 95 inflammation genes and amplified number of reactive microglia within the dentate gyrus. Administration of ex vivo expanded Tregs reduced amyloid burden and reactive glial cells in the dentate gyrus and frontal cortex of 5xFAD-Rag2KO mice. Interrogation of inflammation gene expression documented down-regulation of pro-inflammatory cytokines (IL1A&B, IL6), complement cascade (C1qa, C1qb, C1qc, C4a/b), toll-like receptors (Tlr3, Tlr4 and Tlr7) and microglial activations markers (CD14, Tyrobp,Trem2) following Treg administration.

conclusionsEx vivo expanded Tregs with amplified immunomodulatory function, suppressed neuroinflammation and alleviated AD pathology in vivo. Our results provide preclinical evidences for Treg cell therapy as a potential treatment strategy in AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsDisease Models, AnimalHumansInflammationInterleukin-6Membrane GlycoproteinsMiceMice, TransgenicMicrogliaNeuroinflammatory DiseasesReceptors, ImmunologicT-Lymphocytes, RegulatoryToll-Like Receptor 3Toll-Like Receptor 4Amyloid beta-PeptidesInterleukin-6Membrane GlycoproteinsReceptors, ImmunologicToll-Like Receptor 3Toll-Like Receptor 4Toll-Like Receptor 7Trem2 protein, mouseAdaptive immune systemAlzheimer’s diseaseAmyloid pathologyInflammationMicrogliaRegulatory T cells

Identifiers

PMID36180898
PMCPMC9524037
OpenAlexW4298143552

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.