ArticlePLoS computational biology2015
Three-Dimensional Gradients of Cytokine Signaling between T Cells.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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.
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.
Who cites it
54 citing papers in PubMed, 88 citations in OpenAlex.
- Isotype-switched antibodies originating from tertiary lymphoid structures can antagonize ovarian cancer progression.iScience · 2026Article
- Computational Oncology of Chemotaxis-Driven Tumour-Immune Spatial Patterning and Stability.Bioengineering (Basel, Switzerland) · 2026Article
- Spatial Immune Model of Alveolar Lung Infection (SIMALI) Identifies Structural Determinants of Lung Inflammation.Research square · 2026Article
- CCL19bioRxiv : the preprint server for biology · 2026Article
- Decoding cellular population dynamics through mechanistic modelling and statistical data analysis.NPJ systems biology and applications · 2026Review
- Integrative spatial profiling pipeline for determining TME architectures in archival clinical specimens using CmTSA superplex technology.Cell discovery · 2026Article
- Distinct Cytokine Responses in Central and Systemic Compartments after Subarachnoid Haemorrhage.Translational stroke research · 2025Article
- Altered thymic niche synergistically drives the massive proliferation of malignant thymocytes.eLife · 2025Article
- Neurons as Immunomodulators: From Rapid Neural Activity to Prolonged Regulation of Cytokines and Microglia.Annual review of biomedical engineering · 2025Review
- A flexible systems analysis pipeline for elucidating spatial relationships in the tumor microenvironment linked with cellular phenotypes and patient-level features.Frontiers in immunology · 2025Article
- Effects of virus-induced immunogenic cues on oncolytic virotherapy.Scientific reports · 2024Article
- Diffusion-limited cytokine signaling in T cell populations.iScience · 2024Article
- One CD4+TCR and One CD8+TCR Targeting Autochthonous Neoantigens Are Essential and Sufficient for Tumor Eradication.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system.Lab on a chip · 2024Article
- The spread of interferon-γ in melanomas is highly spatially confined, driving nongenetic variability in tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Tumor-mediated immunosuppression and cytokine spreading affects the relation between EMT and PD-L1 status.Frontiers in immunology · 2023Article
- CD4+ T Cell Regulatory Network Underlies the Decrease in Th1 and the Increase in Anergic and Th17 Subsets in Severe COVID-19.Pathogens (Basel, Switzerland) · 2022Article
- Synthetic cytokine circuits that drive T cells into immune-excluded tumors.Science (New York, N.Y.) · 2022Article
- Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors.Science advances · 2022Article
- Protease-controlled secretion and display of intercellular signals.Nature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune responses are regulated by diffusible mediators, the cytokines, which act at sub-nanomolar concentrations. The spatial range of cytokine communication is a crucial, yet poorly understood, functional property. Both containment of cytokine action in narrow junctions between immune cells (immunological synapses) and global signaling throughout entire lymph nodes have been proposed, but the conditions under which they might occur are not clear. Here we analyze spatially three-dimensional reaction-diffusion models for the dynamics of cytokine signaling at two successive scales: in immunological synapses and in dense multicellular environments. For realistic parameter values, we observe local spatial gradients, with the cytokine concentration around secreting cells decaying sharply across only a few cell diameters. Focusing on the well-characterized T-cell cytokine interleukin-2, we show how cytokine secretion and competitive uptake determine this signaling range. Uptake is shaped locally by the geometry of the immunological synapse. However, even for narrow synapses, which favor intrasynaptic cytokine consumption, escape fluxes into the extrasynaptic space are expected to be substantial (≥20% of secretion). Hence paracrine signaling will generally extend beyond the synapse but can be limited to cellular microenvironments through uptake by target cells or strong competitors, such as regulatory T cells. By contrast, long-range cytokine signaling requires a high density of cytokine producers or weak consumption (e.g., by sparsely distributed target cells). Thus in a physiological setting, cytokine gradients between cells, and not bulk-phase concentrations, are crucial for cell-to-cell communication, emphasizing the need for spatially resolved data on cytokine signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.