The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

Maddaluno, Luigi, Verbrugge, Sue Ellen, Martinoli, Chiara, Matteoli, Gianluca, Chiavelli, Andrea, Zeng, Yiping, Williams, Elizabeth D., Rescigno, Maria, & Cavallaro, Ugo (2009) The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells. Journal of Experimental Medicine, 206(3), pp. 623-635.

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Abstract

The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.

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ID Code: 77756
Item Type: Journal Article
Refereed: Yes
Keywords: Adhesion molecule L1, transendothelial migration, trafficking, dendritic cells, cell adhesion molecules
DOI: 10.1084/jem.20081211
ISSN: 1540-9538
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Molecular Targets (111207)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2009 Maddaluno et al.
Copyright Statement: This article is distributed under the terms of an Attribution–
Noncommercial–Share Alike–No Mirror Sites license for the fi rst six months
after the publication date (see http://www.jem.org/misc/terms.shtml). After six
months it is available under a Creative Commons License (Attribution–Noncommercial–
Share Alike 3.0 Unported license, as described at http://creativecommons
.org/licenses/by-nc-sa/3.0/).
Deposited On: 17 Oct 2014 00:54
Last Modified: 20 Oct 2014 03:04

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