The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells
Open Access
- 9 March 2009
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 206 (3), 623-635
- https://doi.org/10.1084/jem.20081211
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.This publication has 56 references indexed in Scilit:
- Contrasting roles of SPARC-related granuloma in bacterial containment and in the induction of anti–Salmonella typhimurium immunityThe Journal of Experimental Medicine, 2008
- The L1 Cell Adhesion Molecule as a Target for RadioimmunotherapyCancer Biotherapy & Radiopharmaceuticals, 2007
- The adhesion molecule L1 (CD171) promotes melanoma progressionInternational Journal of Cancer, 2006
- Generation and characterization of a mouse lymphatic endothelial cell lineCell and tissue research, 2006
- Isolation and Characterization of A Novel Mouse Lymphatic Endothelial Cell Line: SV-LECLymphatic Research and Biology, 2005
- In vivo Evaluation of 177Lu- and 67/64Cu-Labeled Recombinant Fragments of Antibody chCE7 for Radioimmunotherapy and PET Imaging of L1-CAM-Positive TumorsClinical Cancer Research, 2005
- L1, a novel target of β-catenin signaling, transforms cells and is expressed at the invasive front of colon cancersThe Journal of cell biology, 2005
- Tie2-Cre Transgenic Mice: A New Model for Endothelial Cell-Lineage Analysis in VivoDevelopmental Biology, 2001
- Lymphatic Endothelial Tumors Induced by Intraperitoneal Injection of Incomplete Freund's AdjuvantExperimental Cell Research, 1999
- The L1 Adhesion Molecule Supports αvβ3-Mediated Migration of Human Tumor Cells and Activated T LymphocytesBiochemical and Biophysical Research Communications, 1997