Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation

Nitschké, Maximilian and Aebischer, David and Abadier, Michael and Haener, Simone and Lucic, Matije and Vigl, Benjamin and Luche, Hervé and Fehling, Hans Jörg and Biehlmaier, Oliver and Lyck, Ruth and Halin, Cornelia. (2012) Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation. Blood, 120 (11). pp. 2249-2258.

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Official URL: http://edoc.unibas.ch/47729/

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Dendritic cell (DC) migration via lymphatic vessels to draining lymph nodes (dLNs) is crucial for the initiation of adaptive immunity. We imaged this process by intravital microscopy (IVM) in the ear skin of transgenic mice bearing red-fluorescent vasculature and yellow-fluorescent DCs. DCs within lymphatic capillaries were rarely transported by flow, but actively migrated within lymphatics and were significantly faster than in the interstitium. Pharmacologic blockade of the Rho-associated protein kinase (ROCK), which mediates nuclear contraction and de-adhesion from integrin ligands, significantly reduced DC migration from skin to dLNs in steady-state. IVM revealed that ROCK blockade strongly reduced the velocity of interstitial DC migration, but only marginally affected intralymphatic DC migration. By contrast, during tissue inflammation, ROCK blockade profoundly decreased both interstitial and intralymphatic DC migration. Inhibition of intralymphatic migration was paralleled by a strong upregulation of ICAM-1 in lymphatic endothelium, suggesting that during inflammation ROCK mediates de-adhesion of DC-expressed integrins from lymphatic-expressed ICAM-1. Flow chamber assays confirmed an involvement of lymphatic-expressed ICAM-1 and DC-expressed ROCK in DC crawling on lymphatic endothelium. Overall, our findings further define the role of ROCK in DC migration to dLNs and reveal a differential requirement for ROCK in intralymphatic DC crawling during steady-state and inflammation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Imaging Core Facility (Biehlmaier)
UniBasel Contributors:Biehlmaier, Oliver
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Hematology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Nov 2017 10:42
Deposited On:30 Nov 2017 10:42

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