Evidence map›Paper›PMID 35568856›Full record

ArticleJournal of neuroinflammation2022

Epigenetic regulation of innate immune memory in microglia.

Xiaoming Zhang, Laura Kracht, Antonio M Lerario, Marissa L Dubbelaar, Nieske Brouwer, Evelyn M Wesseling, Erik W G M Boddeke, Bart J L Eggen, Susanne M Kooistra

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

Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

58 citing papers in PubMed, 92 citations in OpenAlex.

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  19. Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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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

9 authors at 3 institutions in 3 countries.

Xiaoming Zhang *Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands.
Laura Kracht *Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands.
Antonio M Lerario *Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA.
Marissa L DubbelaarDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands.
Nieske BrouwerDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands.
Evelyn M WesselingDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands.
Erik W G M BoddekeDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands.
Bart J L Eggen *Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands. b.j.l.eggen@umcg.nl.
Susanne M Kooistra *Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Hpc-FB43, 9713 AV, Groningen, The Netherlands. s.m.kooistra@umcg.nl.ORCID http://orcid.org/0000-0003-0211-8283
University Medical Center Groningen · NLUniversity of Copenhagen · DKUniversity of Michigan · US

Funding

China Scholarship Council 201306300082Nederlandse Organisatie voor Wetenschappelijk Onderzoek #016.161.072Stichting MS Research 16-947
6 · The paper itself

Abstract

backgroundMicroglia are the tissue-resident macrophages of the CNS. They originate in the yolk sac, colonize the CNS during embryonic development and form a self-sustaining population with limited turnover. A consequence of their relative slow turnover is that microglia can serve as a long-term memory for inflammatory or neurodegenerative events.

methodsUsing ATAC-, ChIP- and RNA-sequencing, we characterized the epigenomes and transcriptomes of FACS-purified microglia from mice exposed to different stimuli. A repeated endotoxin challenge (LPS) was used to induce tolerance in microglia, while genotoxic stress (DNA repair deficiency-induced accelerated aging through Ercc1 deficiency) resulted in primed (hypersensitive) microglia.

resultsWhereas the enrichment of permissive epigenetic marks at enhancer regions could explain training (hyper-responsiveness) of primed microglia to an LPS challenge, the tolerized response of microglia seems to be regulated by loss of permissive epigenetic marks. We identify that inflammatory stimuli and accelerated aging as a result of genotoxic stress activate distinct gene networks. These gene networks and associated biological processes are partially overlapping, which is likely driven by specific transcription factor networks, resulting in altered epigenetic signatures and distinct functional (desensitized vs. primed) microglia phenotypes.

conclusionThis study provides insight into epigenetic profiles and transcription factor networks associated with transcriptional signatures of tolerized and trained microglia in vivo, leading to a better understanding of innate immune memory of microglia.

Indexed as

LipopolysaccharidesMicrogliaAnimalsEpigenesis, GeneticImmunity, InnateImmunologic MemoryMiceTranscription FactorsLipopolysaccharidesTranscription FactorsChromatinInnate immunityMicrogliaNeuroinflammationPrimingTolerance

Identifiers

PMID35568856
PMCPMC9107649
OpenAlexW4280541352

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.