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

Vaahtomeri, Kari and Brown, Markus and Hauschild, Robert and de Vries, Ingrid and Leithner, Alexander F and Mehling, Matthias and Kaufmann, Walter A and Sixt, Michael (2017) Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports, 19 (5). 902 -909. ISSN 2211-1247

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Official URL: http://dx.doi.org/10.1016/j.celrep.2017.04.027


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.

Item Type: Article
DOI: 10.1016/j.celrep.2017.04.027
Uncontrolled Keywords: Endothelium, chemokine CCL21, dendritic cell, transmigration, intravasation, lymphatic capillary, triggered secretion, cell-cell contact
Subjects: 500 Science > 570 Life sciences; biology
Research Group: Scientific Service Units > Bioimaging
Scientific Service Units > Scientific Computing
Sixt Group
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 14 Dec 2017 08:13
Last Modified: 14 Dec 2017 08:13
URI: https://repository.ist.ac.at/id/eprint/900

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