ArticleCell systems2023
Quantifying stimulus-response specificity to probe the functional state of macrophages.
Article in Cell systems, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Macrophage response specificity to ligand mixtures is improved by signaling pathway antagonism.Molecular systems biology · 2026Article
- Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons.Seminars in immunopathology · 2026Review
- Linking Adjuvant Immune Stimulation to Spatiotemporal Dynamics via Cross-Scale Photoacoustic Microscopy.Chemical & biomedical imaging · 2026Article
- The authors respond to feedback onFrontiers in oncology · 2026Article
- Agent-specific training directs distinctive immune response againstFrontiers in immunology · 2026Article
- Distinct roles for NF-κB in hematopoietic stem cells and the bone marrow milieu in promoting hematopoietic aging.Cell reports · 2025Article
- Innate Immune Memory is Stimulus Specific.bioRxiv : the preprint server for biology · 2025Article
- A data-driven model of macrophage polarization states reveals an IFN macrophage signature in active Crohn's disease.Frontiers in immunology · 2025Article
- NF-κB: master regulator of cellular responses in health and disease.Immunity & inflammation · 2025Review
- Linking signal input, cell state, and spatial context to inflammatory responses.Current opinion in immunology · 2024Review
- Single-cell stimulus-response gene expression trajectories reveal the stimulus specificities of dynamic responses by single macrophages.Molecular cell · 2024Article
- Examining NF-κB genomic interactions by ChIP-seq and CUT&Tag.bioRxiv : the preprint server for biology · 2024Article
- Dynamical and combinatorial coding by MAPK p38 and NFκB in the inflammatory response of macrophages.Molecular systems biology · 2024Article
- Stimulus-response signaling dynamics characterize macrophage polarization states.Cell systems · 2024Article
- The Blueprint of Logical Decisions in a NF-κB Signaling System.ACS omega · 2024Article
- Reframing macrophage diversity with network motifs.Trends in immunology · 2023Review
- Signaling is the pathway to macrophage function.Trends in immunology · 2023Article
- Uncoding the interdependency of tumor microenvironment and macrophage polarization: insights from a continuous network approach.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Immune sentinel macrophages initiate responses to pathogens via hundreds of immune response genes. Each immune threat demands a tailored response, suggesting that the capacity for stimulus-specific gene expression is a key functional hallmark of healthy macrophages. To quantify this property, termed "stimulus-response specificity" (SRS), we developed a single-cell experimental workflow and analytical approaches based on information theory and machine learning. We found that the response specificity of macrophages is driven by combinations of specific immune genes that show low cell-to-cell heterogeneity and are targets of separate signaling pathways. The "response specificity profile," a systematic comparison of multiple stimulus-response distributions, was distinctly altered by polarizing cytokines, and it enabled an assessment of the functional state of macrophages. Indeed, the response specificity profile of peritoneal macrophages from old and obese mice showed characteristic differences, suggesting that SRS may be a basis for measuring the functional state of innate immune cells. A record of this paper's transparent peer review process is included in the supplemental information.
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