Evidence map›Paper›PMID 33436596›Full record

ArticleNature communications2021

Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells.

Andrés R Muñoz-Rojas, Ilana Kelsey, Jenna L Pappalardo, Meibin Chen, Kathryn Miller-Jensen

Abstract read
In one paragraph

Article in Nature communications, 2021. 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
–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

58 citing papers in PubMed.

  1. Review
  2. Regulation of immune signal integration and memory by inflammation-induced chromosome conformation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Tissue signatures of human macrophages during homeostasis and activation.Journal of immunology (Baltimore, Md. : 1950) · 2026
    Article
  8. Article
  9. bioRxiv : the preprint server for biology · 2026
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Innate Immune Memory is Stimulus Specific.bioRxiv : the preprint server for biology · 2025
    Article
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

5 authors.

Andrés R Muñoz-RojasDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0000-0002-1251-723X
Ilana KelseyDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0000-0001-8679-6094
Jenna L PappalardoDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Meibin ChenDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Kathryn Miller-JensenDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA. kathryn.miller-jensen@yale.edu.ORCID 0000-0002-7233-0100

Funding

Systems analysis of cell-to-cell variability and signaling-transcription factor motifs regulating macrophage responses to conflicting environmental cuesR01GM123011 · NIGMS · YALE UNIVERSITY · PI MILLER-JENSEN, KATHRYN · 2017 to 2025
$2.5M
NIGMS NIH HHS R01 GM123011
6 · The paper itself

Abstract

Macrophages are innate immune cells that contribute to fighting infections, tissue repair, and maintaining tissue homeostasis. To enable such functional diversity, macrophages resolve potentially conflicting cues in the microenvironment via mechanisms that are unclear. Here, we use single-cell RNA sequencing to explore how individual macrophages respond when co-stimulated with inflammatory stimuli LPS and IFN-γ and the resolving cytokine IL-4. These co-stimulated macrophages display a distinct global transcriptional program. However, variable negative cross-regulation between some LPS + IFN-γ-specific and IL-4-specific genes results in cell-to-cell heterogeneity in transcription. Interestingly, negative cross-regulation leads to mutually exclusive expression of the T-cell-polarizing cytokine genes Il6 and Il12b versus the IL-4-associated factors Arg1 and Chil3 in single co-stimulated macrophages, and single-cell secretion measurements show that these specialized functions are maintained for at least 48 h. This study suggests that increasing functional diversity in the population is one strategy macrophages use to respond to conflicting environmental cues.

Indexed as

Cell PolarityAnimalsArginaseFemaleGene Expression RegulationInterferon-gammaInterleukin-12Interleukin-6LipopolysaccharidesMachine LearningMacrophagesMaleMiceMice, Inbred C57BLNeural Networks, ComputerOdds RatioArginaseInterferon-gammaInterleukin-12Interleukin-6LipopolysaccharidesTranscription Factors

Identifiers

PMID33436596
PMCPMC7804107

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.