title: The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells.
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.
authors.affiliation: The FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Maddaluno
authors.forename: Sue Ellen
authors.initials: SE
authors.lastname: Verbrugge
authors.forename: Chiara
authors.initials: C
authors.lastname: Martinoli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Matteoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Chiavelli
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zeng
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Williams
authors.forename: Maria
authors.initials: M
authors.lastname: Rescigno
authors.forename: Ugo
authors.initials: U
authors.lastname: Cavallaro
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D014409:Tumor Necrosis Factor-alpha