ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Network Analysis Reveals a Distinct Axis of Macrophage Activation in Response to Conflicting Inflammatory Cues.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- Macrophage metabolism reprogramming in sepsis: Pathogenesis and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Cellular and molecular signals of cardiac wound healing after myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2026Review
- Sequential polarization of macrophages: an immunomodulatory strategy for novel bone repair materials.Regenerative biomaterials · 2026Review
- Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.Frontiers in immunology · 2026Review
- Experimental and computational studies of IL-6 signaling in endothelial cells under hypoxia serum starvation conditions.Cytokine · 2025Article
- Multi-cellular network model predicts alterations in glomerular endothelial structure in diabetic kidney disease.PLoS computational biology · 2025Article
- Logic-based modeling of biological networks with Netflux.PLoS computational biology · 2025Article
- Multi-Scale Multi-Cell Computational Model of Inflammation-Mediated Aortic Remodeling in Hypertension.Annals of biomedical engineering · 2025Article
- Linking signal input, cell state, and spatial context to inflammatory responses.Current opinion in immunology · 2024Review
- Fatty acid metabolism of immune cells: a new target of tumour immunotherapy.Cell death discovery · 2024Review
- Getting everyone to agree on gene signatures for murine macrophage polarization in vitro.PloS one · 2024Article
- Reframing macrophage diversity with network motifs.Trends in immunology · 2023Review
- An in vitro model of the macrophage-endothelial interface to characterize CAR T-cell induced cytokine storm.Scientific reports · 2023Article
- Experiment-based computational model predicts that IL-6 classic and trans-signaling exhibit similar potency in inducing downstream signaling in endothelial cells.NPJ systems biology and applications · 2023Article
- A computational bridge between traction force microscopy and tissue contraction.Journal of applied physics · 2023Article
- Article
- Experiment-based Computational Model Predicts that IL-6 Trans-Signaling Plays a Dominant Role in IL-6 mediated signaling in Endothelial Cells.bioRxiv : the preprint server for biology · 2023Article
- Organogermanium THGP Induces Differentiation into M1 Macrophages and Suppresses the Proliferation of Melanoma Cells via Phagocytosis.International journal of molecular sciences · 2023Article
- The cardiac wound healing response to myocardial infarction.WIREs mechanisms of disease · 2023Review
- Vascular smooth muscle cell mechanotransduction through serum and glucocorticoid inducible kinase-1 promotes interleukin-6 production and macrophage accumulation in murine hypertension.JVS-vascular science · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophages are subject to a wide range of cytokine and pathogen signals in vivo, which contribute to differential activation and modulation of inflammation. Understanding the response to multiple, often-conflicting cues that macrophages experience requires a network perspective. In this study, we integrate data from literature curation and mRNA expression profiles obtained from wild type C57/BL6J mice macrophages to develop a large-scale computational model of the macrophage signaling network. In response to stimulation across all pairs of nine cytokine inputs, the model predicted activation along the classic M1-M2 polarization axis but also a second axis of macrophage activation that distinguishes unstimulated macrophages from a mixed phenotype induced by conflicting cues. Along this second axis, combinations of conflicting stimuli, IL-4 with LPS, IFN-γ, IFN-β, or TNF-α, produced mutual inhibition of several signaling pathways, e.g., NF-κB and STAT6, but also mutual activation of the PI3K signaling module. In response to combined IFN-γ and IL-4, the model predicted genes whose expression was mutually inhibited, e.g.,
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Registered trials
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 Socratic graph.