The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells.
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.
Maddaluno
Luigi
L
The FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Verbrugge
Sue Ellen
SE
Martinoli
Chiara
C
Matteoli
Gianluca
G
Chiavelli
Andrea
A
Zeng
Yiping
Y
Williams
Elizabeth D
ED
Rescigno
Maria
M
Cavallaro
Ugo
U
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
D039842:Neural Cell Adhesion Molecule L1; D014409:Tumor Necrosis Factor-alpha