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Cited by 86Lymphatic System and DiseasesChemokine receptors and signalingCell Adhesion Molecules Research

Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia

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Vaahtomeri, Kari, Brown, Markus, Hauschild, Robert, De Vries, Ingrid, Leithner, Alexander Franz, Mehling, Matthias, Kaufmann, Walter Anton, Sixt, Michael·2017·Cell Reports
DOI 10.1016/j.celrep.2017.04.027PMC PMC5437727
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Abstract

Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.

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  • CCL21 is responsible for the arrest of DCs near the flaps between neighboring LECs and their subsequent entry into the vessel lumen.

    “In addition to its role in the attraction of T cells and DCs toward initial LVs, CCL21 is responsible for the arrest of DCs near the flaps between neighboring LECs and their subsequent entry into the vessel lumen (108).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [108]

    In Results and Discussion (page not provided), the paper reports that DC-associated CCL21 accumulates near LEC–LEC junctions and that CCL21 secretion promotes DC transmigration. It proposes that local release may guide DCs to an entry portal and help them enter the lumen, but does not establish that CCL21 arrests DCs near the flaps between neighboring LECs. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • DC interaction with LECs in initial LVs induces rapid mobilization of CCL21 from intracellular stores in LECs and accumulation of CCL21 in extracellular puncta on the basolateral side of the LEC.

    “In this regard, DC interaction with LECs in initial LVs induces the rapid mobilization of CCL21 from intracellular stores in LECs and accumulation of CCL21 in extracellular puncta on the basolateral side of the LEC (108) ( Figure 3b ).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [108]

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Authors
Vaahtomeri, K., Brown, M., Hauschild, R., De Vries, I., Leithner, A. F., Mehling, M., Kaufmann, W. A., & Sixt, M.
Affiliations
  • University of Helsinki (FI)
  • Institute of Science and Technology Austria (AT)
Corresponding author
  • Vaahtomeri, Kari
  • Sixt, Michael
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2017-05
Volume
19
Issue
5
Pages
902-909
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2017.04.027
PMC
PMC5437727
OpenAlex
W2611717599
Cited by
86
References
2
Citations by year
2026: 7 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 15 · 2020: 14 · 2019: 10 · 2018: 13 · 2017: 5
FWCI
5.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Sigrid Juselius Foundation
  • Academy of Finland (287853)
  • European Research Council (ERC GA 281556)
  • Austrian Science Foundation
  • FWF (Y564-B12 START)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
CCL21, lymphatic endothelium, transendothelial migration, chemokine secretion, trans-Golgi network, calcium signaling, cell-cell contact, lymphatic capillaries, lymphocyte migration
MeSH terms
Animals, Dendritic Cells, Endothelium, Lymphatic, Female, Intercellular Junctions, Male, Mice, Inbred C57BL, Calcium Signaling, Endothelial Cells, Mice, Chemokine CCL21, Transendothelial and Transepithelial Migration

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