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

Luigi Maddaluno, Sue Ellen Verbrugge, Chiara Martinoli, Gianluca Matteoli, Andrea Chiavelli, Yiping Zeng, Elizabeth Williams, Maria Rescigno, Ugo Cavallaro

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56 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)623 - 635
Number of pages13
JournalJournal of Experimental Medicine
Volume206
Issue number3
DOIs
Publication statusPublished - 2009

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