Evidence map›Paper›PMID 34551303›Full record

ArticleCell reports2021

Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory response.

Amanda F Alexander, Ilana Kelsey, Hannah Forbes, Kathryn Miller-Jensen

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

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  11. Impact of Black Soldier Fly Larvae Oil on Immunometabolic Processes.International journal of molecular sciences · 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

4 authors at 1 institution in 1 country.

Amanda F AlexanderDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Ilana KelseyDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Hannah ForbesDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Kathryn Miller-JensenDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA; Systems Biology Institute, Yale University, New Haven, CT 06511, USA. Electronic address: kathryn.miller-jensen@yale.edu.
Yale University · US

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

Following Toll-like receptor 4 (TLR4) stimulation of macrophages, negative feedback mediated by the anti-inflammatory cytokine interleukin-10 (IL-10) limits the inflammatory response. However, extensive cell-to-cell variability in TLR4-stimulated cytokine secretion raises questions about how negative feedback is robustly implemented. To explore this, we characterize the TLR4-stimulated secretion program in primary murine macrophages using a single-cell microwell assay that enables evaluation of functional autocrine IL-10 signaling. High-dimensional analysis of single-cell data reveals three tiers of TLR4-induced proinflammatory activation based on levels of cytokine secretion. Surprisingly, while IL-10 inhibits TLR4-induced activation in the highest tier, it also contributes to the TLR4-induced activation threshold by regulating which cells transition from non-secreting to secreting states. This role for IL-10 in restraining TLR4 inflammatory activation is largely mediated by intermediate interferon (IFN)-β signaling, while TNF likely mediates response resolution by IL-10. Thus, cell-to-cell variability in cytokine regulatory motifs provides a means to tailor the TLR4-induced inflammatory response.

Indexed as

AnimalsAntibodiesChemokine CCL5FemaleInterferon-betaInterleukin-10LipopolysaccharidesMacrophagesMiceMice, Inbred C57BLReceptors, Interleukin-10Recombinant ProteinsSignal TransductionSingle-Cell AnalysisToll-Like Receptor 4Tumor Necrosis Factor-alphaAntibodiesChemokine CCL5Interferon-betaInterleukin-10LipopolysaccharidesReceptors, Interleukin-10Recombinant ProteinsToll-Like Receptor 4Tumor Necrosis Factor-alphaIL-10macrophagesingle-cell measurementsTLR4 signaling

Identifiers

PMID34551303
PMCPMC8995750
OpenAlexW3201602351

What OpenQuestion holds

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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.