ArticleScience signaling2015
Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 154 citations in OpenAlex.
- Heritable single-cell gene expression states shape functional variability in innate immune responses.bioRxiv : the preprint server for biology · 2026Article
- Nested Nanowell Arrays for High-Throughput Quantitative Analysis of Cytokines from Single Macrophages.ACS nano medicine · 2026Article
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- Macrophage Paracrine Signalling Differentially Affects Fibroblast-Induced Collagenous Tissue Remodelling.Tissue engineering and regenerative medicine · 2026Article
- Decoding the temporal dimension of innate immunity in intravesical BCG therapy.Frontiers in immunology · 2026Article
- Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026Review
- Microsystem technologies for accelerating the discovery and translation of immunotherapies.Nature reviews. Drug discovery · 2026Review
- Absence of c-Maf and IL-10 enables type I IFN enhancement of innate responses to LPS in alveolar macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Article
- Agent-based model predicts that layered structure and 3D movement work synergistically to reduce bacterial load in 3D in vitro models of tuberculosis granuloma.PLoS computational biology · 2024Article
- Absence of c-Maf and IL-10 enables Type I IFN enhancement of innate responses to low-dose LPS in alveolar macrophages.bioRxiv : the preprint server for biology · 2024Article
- Current Progress in the Science of Novel Adjuvant Nano-Vaccine-Induced Protective Immune Responses.Pathogens (Basel, Switzerland) · 2024Review
- Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Identification of druggable regulators of cell secretion via a kinome-wide screen and high-throughput immunomagnetic cell sorting.Nature biomedical engineering · 2024Article
- In silico agent-based modeling approach to characterize multiple in vitro tuberculosis infection models.PloS one · 2024Article
- Evidence of collective influence in innate sensing using fluidic force microscopy.Frontiers in immunology · 2024Article
- Macro- and micro-scale culture environment differentially regulate the effects of crowding on macrophage function.Biotechnology and bioengineering · 2024Article
- The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2 cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Reframing macrophage diversity with network motifs.Trends in immunology · 2023Review
- Processing stimulus dynamics by the NF-κB network in single cells.Experimental & molecular medicine · 2023Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Macrophages not only produce multiple cytokines but also respond to multiple cytokines, which likely shapes the ultimate response of the population. To determine the role of paracrine signaling in shaping the profile of inflammatory cytokines secreted by macrophages in response to stimulation of Toll-like receptor 4 (TLR4) with lipopolysaccharide (LPS), we combined multiplexed, microwell-based measurements of cytokine secretion by single cells with analysis of cytokine secretion by cell populations. Loss of paracrine signaling as a result of cell isolation reduced the secretion by macrophage-like U937 cells and human monocyte-derived macrophages (MDMs) of a subset of LPS-stimulated cytokines, including interleukin-6 (IL-6) and IL-10. Graphical Gaussian modeling (GGM) of the single-cell data defined a regulatory network of paracrine signals, which was validated experimentally in the population through antibody-mediated neutralization of individual cytokines. Tumor necrosis factor-α (TNF-α) was the most influential cytokine in the GGM network. Paracrine signaling by TNF-α secreted from a small subpopulation of "high-secreting" cells was necessary, but not sufficient, for the secretion of large amounts of IL-6 and IL-10 by the cell population. Decreased relative IL-10 secretion by isolated MDMs was linked to increased TNF-α secretion, suggesting that inhibition of the inflammatory response also depends on paracrine signaling. Our results reveal a previously uncharacterized role for cell-to-cell communication within a population in coordinating a rapid innate immune response despite underlying cell-to-cell heterogeneity.
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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.