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

Nitschké, Maximilian; Aebischer, David; Abadier, Michael; Haener, Simone; Lucic, Matije; Vigl, Benjamin; Luche, Hervé; Fehling, Hans Jörg; Biehlmaier, Oliver; Lyck, Ruth; Halin, Cornelia (2012). Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation. Blood, 120(11), pp. 2249-58. Washington, D.C.: American Society of Hematology 10.1182/blood-2012-03-417923

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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 up-regulation 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Abadier, Michael Madgy Labib and Lyck, Ruth

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:36

Last Modified:

23 Oct 2014 17:36

Publisher DOI:

10.1182/blood-2012-03-417923

PubMed ID:

22855606

Web of Science ID:

000309044200017

URI:

https://boris.unibe.ch/id/eprint/14680 (FactScience: 221779)

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