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Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration

Chemokine-guided leukocyte migration is a hallmark of the immune system to cope with invading pathogens. Intruder confronted dendritic cells (DCs) induce the expression of the chemokine receptor CCR7, which enables them to sense and migrate along chemokine gradients to home to draining lymph nodes,...

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Detalles Bibliográficos
Autores principales: Artinger, Marc, Gerken, Oliver J., Purvanov, Vladimir, Legler, Daniel F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234131/
https://www.ncbi.nlm.nih.gov/pubmed/35769489
http://dx.doi.org/10.3389/fimmu.2022.913366
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author Artinger, Marc
Gerken, Oliver J.
Purvanov, Vladimir
Legler, Daniel F.
author_facet Artinger, Marc
Gerken, Oliver J.
Purvanov, Vladimir
Legler, Daniel F.
author_sort Artinger, Marc
collection PubMed
description Chemokine-guided leukocyte migration is a hallmark of the immune system to cope with invading pathogens. Intruder confronted dendritic cells (DCs) induce the expression of the chemokine receptor CCR7, which enables them to sense and migrate along chemokine gradients to home to draining lymph nodes, where they launch an adaptive immune response. Chemokine-mediated DC migration is recapitulated and intensively studied in 3D matrix migration chambers. A major caveat in the field is that chemokine gradient formation and maintenance in such 3D environments is generally not assessed. Instead, fluorescent probes, mostly labelled dextran, are used as surrogate molecules, thereby neglecting important electrochemical properties of the chemokines. Here, we used site-specifically, fluorescently labelled CCL19 and CCL21 to study the establishment and shape of the chemokine gradients over time in the 3D collagen matrix. We demonstrate that CCL19 and particularly CCL21 establish stable, but short-distance spanning gradients with an exponential decay-like shape. By contrast, dextran with its neutral surface charge forms a nearly linear gradient across the entire matrix. We show that the charged C-terminal tail of CCL21, known to interact with extracellular matrix proteins, is determinant for shaping the chemokine gradient. Importantly, DCs sense differences in the shape of CCL19 and CCL21 gradients, resulting in distinct spatial migratory responses.
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spelling pubmed-92341312022-06-28 Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration Artinger, Marc Gerken, Oliver J. Purvanov, Vladimir Legler, Daniel F. Front Immunol Immunology Chemokine-guided leukocyte migration is a hallmark of the immune system to cope with invading pathogens. Intruder confronted dendritic cells (DCs) induce the expression of the chemokine receptor CCR7, which enables them to sense and migrate along chemokine gradients to home to draining lymph nodes, where they launch an adaptive immune response. Chemokine-mediated DC migration is recapitulated and intensively studied in 3D matrix migration chambers. A major caveat in the field is that chemokine gradient formation and maintenance in such 3D environments is generally not assessed. Instead, fluorescent probes, mostly labelled dextran, are used as surrogate molecules, thereby neglecting important electrochemical properties of the chemokines. Here, we used site-specifically, fluorescently labelled CCL19 and CCL21 to study the establishment and shape of the chemokine gradients over time in the 3D collagen matrix. We demonstrate that CCL19 and particularly CCL21 establish stable, but short-distance spanning gradients with an exponential decay-like shape. By contrast, dextran with its neutral surface charge forms a nearly linear gradient across the entire matrix. We show that the charged C-terminal tail of CCL21, known to interact with extracellular matrix proteins, is determinant for shaping the chemokine gradient. Importantly, DCs sense differences in the shape of CCL19 and CCL21 gradients, resulting in distinct spatial migratory responses. Frontiers Media S.A. 2022-06-13 /pmc/articles/PMC9234131/ /pubmed/35769489 http://dx.doi.org/10.3389/fimmu.2022.913366 Text en Copyright © 2022 Artinger, Gerken, Purvanov and Legler https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Artinger, Marc
Gerken, Oliver J.
Purvanov, Vladimir
Legler, Daniel F.
Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration
title Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration
title_full Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration
title_fullStr Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration
title_full_unstemmed Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration
title_short Distinct Fates of Chemokine and Surrogate Molecule Gradients: Consequences for CCR7-Guided Dendritic Cell Migration
title_sort distinct fates of chemokine and surrogate molecule gradients: consequences for ccr7-guided dendritic cell migration
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234131/
https://www.ncbi.nlm.nih.gov/pubmed/35769489
http://dx.doi.org/10.3389/fimmu.2022.913366
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