Evidence map›Paper›PMID 39863579›Full record

ArticleNature communications2025

Genetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically.

Mingming Zhao, Dragana Jankovic, Verena M Link, Camila Oliveira Silva Souza, Katherine M Hornick, Oyebola Oyesola, Yasmine Belkaid, Justin Lack, Png Loke

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Mingming ZhaoType 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2092-9928
Dragana JankovicType 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7360-1809
Verena M LinkMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3207-312X
Camila Oliveira Silva SouzaType 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-6922-5270
Katherine M HornickNIAID Collaborative Bioinformatics Resource, Integrated Data Sciences Section, Research Technology Branch, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA.
Oyebola OyesolaType 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5347-7502
Yasmine BelkaidMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9962-3571
Justin LackNIAID Collaborative Bioinformatics Resource, Integrated Data Sciences Section, Research Technology Branch, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA.
Png LokeType 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. Png.Loke@nih.gov.ORCID http://orcid.org/0000-0002-6211-3292

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

How macrophages in the tissue environment integrate multiple stimuli depends on the genetic background of the host, but this is still poorly understood. We investigate IL-4 activation of male C57BL/6 and BALB/c strain specific in vivo tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with induced genes associated with more super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling reveals C57BL/6 specific enrichment of NF-κB, IRF, and STAT motifs. Additionally, IL-4-activated C57BL/6 TRMs demonstrate an augmented synergistic response upon in vitro lipopolysaccharide (LPS) exposure, despite naïve BALB/c TRMs displaying a more robust transcriptional response to LPS. Single-cell RNA sequencing (scRNA-seq) analysis of mixed bone marrow chimeras indicates that transcriptional differences and synergy are cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming resulting in strain specific synergistic responses to LPS exposure.

Indexed as

Epigenesis, GeneticGenetic VariationInterleukin-4LipopolysaccharidesMacrophagesAnimalsMacrophage ActivationMaleMiceMice, Inbred BALB CMice, Inbred C57BLSingle-Cell AnalysisSpecies SpecificityIl4 protein, mouseInterleukin-4Lipopolysaccharides

Identifiers

PMID39863579
PMCPMC11762786

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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.