Evidence map›Paper›PMID 28973837›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2018

EZH2 Modulates the DNA Methylome and Controls T Cell Adhesion Through Junctional Adhesion Molecule A in Lupus Patients.

Pei-Suen Tsou, Patrick Coit, Nathan C Kilian, Amr H Sawalha

Open access · greenAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

35 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
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  4. Inducible deletion ofiScience · 2024
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  17. The Roles of Junctional Adhesion Molecules (JAMs) in Cell Migration.Frontiers in cell and developmental biology · 2022
    Review
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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

4 authors at 1 institution in 1 country.

Pei-Suen TsouUniversity of Michigan, Ann Arbor.
Patrick CoitUniversity of Michigan, Ann Arbor.
Nathan C KilianUniversity of Michigan, Ann Arbor.
Amr H SawalhaUniversity of Michigan, Ann Arbor.
University of Michigan–Ann Arbor · US

Funding

TRAINING OF ARTHRITIS RESEARCH SCIENTISTST32AR007080 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason Knight · 1986 to 2026
$6.3M
Role of DNA methylation in lupusR01AI097134 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Amr H Sawalha · 2013 to 2026
$4.5M
NIAID NIH HHS R01 AI097134NIAMS NIH HHS T32 AR007080
6 · The paper itself

Abstract

objectiveEZH2 is an epigenetic regulator that mediates H3K27 trimethylation (H3K27me3) and modulates DNA methylation. The aim of this study was to characterize the role of EZH2 in CD4+ T cells in the pathogenesis of systemic lupus erythematosus.

methodsEZH2 expression levels were determined in CD4+ T cells isolated from lupus patients and healthy controls. The epigenetic effects of EZH2 overexpression in CD4+ T cells were evaluated using a genome-wide DNA methylation approach. Gene expression profiles and microRNAs (miRNAs) were assessed by quantitative polymerase chain reaction, while protein expression was examined by Western blotting. A cell adhesion assay was used to assess adhesion of CD4+ T cells to human microvascular endothelial cells.

resultsEZH2 and H3K27me3 levels were increased in CD4+ T cells from lupus patients compared to healthy controls. T cell production of EZH2 was down-regulated in the presence of miR-26a and miR-101, and levels of both miRNAs were reduced in lupus CD4+ T cells. Overexpression of EZH2 induced in CD4+ T cells resulted in significant DNA methylation changes. Genes involved in leukocyte adhesion and migration, including F11R (which encodes junctional adhesion molecule A [JAM-A]), became hypomethylated in CD4+ T cells when EZH2 was overexpressed. Overexpression of EZH2 resulted in increases in JAM-A expression and CD4+ T cell adhesion. Preincubation of EZH2-transfected CD4+ T cells with neutralizing antibodies against JAM-A significantly blunted cell adhesion. Similarly, CD4+ T cells from lupus patients overexpressed JAM-A and adhered significantly more to endothelial cells than to T cells from healthy controls. Blocking JAM-A or EZH2 significantly reduced the capacity of lupus CD4+ T cells to adhere to endothelial cells.

conclusionThe results of this study identify a novel role of EZH2 in T cell adhesion mediated by epigenetic remodeling and up-regulation of JAM-A. Blockade of EZH2 or JAM-A might have therapeutic potential by acting to reduce T cell adhesion, migration, and extravasation in patients with lupus.

Indexed as

AdultBlotting, WesternCD4-Positive T-LymphocytesCell AdhesionCell Adhesion MoleculesCell Culture TechniquesDNADNA MethylationEnhancer of Zeste Homolog 2 ProteinFemaleGene Expression ProfilingGene Expression RegulationHumansLupus Erythematosus, SystemicMicroRNAsMiddle AgedCell Adhesion MoleculesDNAEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanF11R protein, humanMicroRNAsReceptors, Cell Surface

Identifiers

PMID28973837
PMCPMC5745285
OpenAlexW2763761818

What OpenQuestion holds

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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.