ArticleScientific reports2019
Sequential conditioning-stimulation reveals distinct gene- and stimulus-specific effects of Type I and II IFN on human macrophage functions.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Systemic reprogramming of monocytes in Crohn's disease promotes their intestinal inflammatory function.JCI insight · 2026Article
- IFNγ shapes macrophage inflammatory responses by STAT1 isoform-specific epigenetic and transcriptional mechanisms.BMC genomics · 2026Article
- Exaggerated IFN-I Response in Long COVID PBMCs Following Exposure to Viral Mimics.Journal of clinical immunology · 2025Article
- AI-Driven Analysis Unveils Functional Dynamics of Müller Cells in Retinal Autoimmune Inflammation.bioRxiv : the preprint server for biology · 2025Article
- Cytosine-to-uracil RNA editing is upregulated by pro-inflammatory stimulation of myeloid cells.bioRxiv : the preprint server for biology · 2025Article
- The role of type I interferon signaling in myeloid anti-tumor immunity.Frontiers in immunology · 2025Review
- NF-κB: master regulator of cellular responses in health and disease.Immunity & inflammation · 2025Review
- Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.Cell reports · 2024Article
- Transcriptional control of interferon-stimulated genes.The Journal of biological chemistry · 2024Review
- Stimulus-response signaling dynamics characterize macrophage polarization states.Cell systems · 2024Article
- Spatial, transcriptomic and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.bioRxiv : the preprint server for biology · 2024Article
- Quantifying stimulus-response specificity to probe the functional state of macrophages.Cell systems · 2023Article
- The tempo and mode of gene regulatory programs during bacterial infection.Cell reports · 2022Article
- Functional inference of gene regulation using single-cell multi-omics.Cell genomics · 2022Article
- Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance.Annual review of immunology · 2022Review
- Article
- System-wide identification of myeloid markers of TB disease and HIV-induced reactivation in the macaque model of Mtb infection and Mtb/SIV co-infection.Frontiers in immunology · 2022Article
- Review
- Identifying the combinatorial control of signal-dependent transcription factors.PLoS computational biology · 2021Article
- IRF1 governs the differential interferon-stimulated gene responses in human monocytes and macrophages by regulating chromatin accessibility.Cell reports · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophages orchestrate immune responses by sensing and responding to pathogen-associated molecules. These responses are modulated by prior conditioning with cytokines such as interferons (IFNs). Type I and II IFN have opposing functions in many biological scenarios, yet macrophages directly stimulated with Type I or II IFN activate highly overlapping gene expression programs. We hypothesized that a sequential conditioning-stimulation approach would reveal with greater specificity the differential effects of Type I and II IFN on human macrophages. By first conditioning with IFN then stimulating with toll-like receptor ligands and cytokines, followed by genome-wide RNA-seq analysis, we identified 713 genes whose expression was unaffected by IFN alone but showed potentiated or diminished responses to a stimulus after conditioning. For example, responses to the cytokine TNF were restricted by Type II IFN conditioning but potentiated by Type I IFN conditioning. We observed that the effects of IFN were not uniformly pro- or anti-inflammatory, but highly gene-specific and stimulus-specific. By assessing expression levels of key signal transducers and characterizing chromatin accessibility by ATAC-seq, we identify the likely molecular mechanisms underlying Type I and Type II-specific effects, distinguishing between modulation of cytoplasmic signaling networks and the nuclear epigenome that synergistically regulate macrophage immune responses.
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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 OpenQuestion graph.