ArticleJournal of immunology (Baltimore, Md. : 1950)2017
A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
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- Atherosclerosis increases adventitial pressure and limits solute transport via fluid-balance mechanisms.Biomechanics and modeling in mechanobiology · 2025Article
- Atypical chemokine receptors in the immune system.Nature reviews. Immunology · 2024Review
- 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
- New tools for immunologists: models of lymph node function from cells to tissues.Frontiers in immunology · 2023Review
- Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells.International journal of molecular sciences · 2022Article
- Review
- Autologous gradient formation under differential interstitial fluid flow environments.Biophysica · 2022Article
- Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system.Materials today. Bio · 2022Review
- Generation of stable advective-diffusive chemokine gradients in a three-dimensional hydrogel.AIP advances · 2022Article
- Advancing therapies for viral infections using mechanistic computational models of the dynamic interplay between the virus and host immune response.Current opinion in virology · 2021Review
- QSP-IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno-Oncology Applications.CPT: pharmacometrics & systems pharmacology · 2020Article
- The Biophysics of Lymphatic Transport: Engineering Tools and Immunological Consequences.iScience · 2019Review
- Quantification of the Whole Lymph Node Vasculature Based on Tomography of the Vessel Corrosion Casts.Scientific reports · 2019Article
- A Computational Model of Neoadjuvant PD-1 Inhibition in Non-Small Cell Lung Cancer.The AAPS journal · 2019Article
- Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment.Processes (Basel, Switzerland) · 2019Article
- CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention.Frontiers in cell and developmental biology · 2019Review
- Chemokine Transport Dynamics and Emerging Recognition of Their Role in Immune Function.Current opinion in biomedical engineering · 2018Article
- Integrative Computational Modeling of the Lymph Node Stromal Cell Landscape.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations. The mechanisms underpinning the establishment and regulation of these gradients are poorly understood. In this article, we have incorporated multiple biochemical processes describing the CCL19-CCL21-CCR7-ACKR4 network into our model of LN fluid flow to establish a computational model to investigate intranodal chemokine gradients. Importantly, the model recapitulates CCL21 gradients observed experimentally in B cell follicles and interfollicular regions, building confidence in its ability to accurately predict intranodal chemokine distribution. Parameter variation analysis indicates that the directionality of these gradients is robust, but their magnitude is sensitive to these key parameters: chemokine production, diffusivity, matrix binding site availability, and CCR7 abundance. The model indicates that lymph flow shapes intranodal CCL21 gradients, and that CCL19 is functionally important at the boundary between B cell follicles and the T cell area. It also predicts that ACKR4 in LNs prevents CCL19/CCL21 accumulation in efferent lymph, but does not control intranodal gradients. Instead, it attributes the disrupted interfollicular CCL21 gradients observed in
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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.