In vivo analysis of uropod function during physiological T cell trafficking

Soriano, Silvia F; Hons, Miroslav; Schumann, Kathrin; Kumar, Varsha; Dennier, Timo J; Lyck, Ruth; Sixt, Michael; Stein, Jens V (2011). In vivo analysis of uropod function during physiological T cell trafficking. Journal of immunology, 187(5), pp. 2356-64. Bethesda, Md.: American Association of Immunologists 10.4049/jimmunol.1100935

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Migrating lymphocytes acquire a polarized phenotype with a leading and a trailing edge, or uropod. Although in vitro experiments in cell lines or activated primary cell cultures have established that Rho-p160 coiled-coil kinase (ROCK)-myosin II-mediated uropod contractility is required for integrin de-adhesion on two-dimensional surfaces and nuclear propulsion through narrow pores in three-dimensional matrices, less is known about the role of these two events during the recirculation of primary, nonactivated lymphocytes. Using pharmacological antagonists of ROCK and myosin II, we report that inhibition of uropod contractility blocked integrin-independent mouse T cell migration through narrow, but not large, pores in vitro. T cell crawling on chemokine-coated endothelial cells under shear was severely impaired by ROCK inhibition, whereas transendothelial migration was only reduced through endothelial cells with high, but not low, barrier properties. Using three-dimensional thick-tissue imaging and dynamic two-photon microscopy of T cell motility in lymphoid tissue, we demonstrated a significant role for uropod contractility in intraluminal crawling and transendothelial migration through lymph node, but not bone marrow, endothelial cells. Finally, we demonstrated that ICAM-1, but not anatomical constraints or integrin-independent interactions, reduced parenchymal motility of inhibitor-treated T cells within the dense lymphoid microenvironment, thus assigning context-dependent roles for uropod contraction during lymphocyte recirculation.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Hons, Miroslav; Lyck, Ruth and Stein, Jens Volker

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:23

Last Modified:

06 Dec 2013 13:28

Publisher DOI:

10.4049/jimmunol.1100935

PubMed ID:

21795598

Web of Science ID:

000294059500040

URI:

https://boris.unibe.ch/id/eprint/7805 (FactScience: 213146)

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