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

Maddaluno L, Verbrugge SE, Martinoli C, Matteoli G, Chiavelli A, Zeng Y, Williams ED, Rescigno M, Cavallaro U - J. Exp. Med. (2009)

Bottom Line: 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.Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs.

View Article: PubMed Central - PubMed

Affiliation: The FIRC Institute of Molecular Oncology, 20139 Milan, Italy.

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.

Show MeSH

Related in: MedlinePlus

Ablation of L1 in DCs fromTie2-Cre;L1floxed mice. (A)CD11c-positive cells from the lymph nodes of C57BL/6 mice (left) weregated and analyzed for L1 expression (right). Background staining wasdetermined with a control isotype-matched antibody (black line). Theexperiment was repeated with lymph nodes from five individual mice withsimilar results, and the figure refers to one representative analysis ofone mouse. (B) FACS analysis of CD11c and L1 coexpression in bonemarrow–derived DCs from L1floxedand Tie2-Cre;L1floxed mice. The experimentwas repeated with similar results on four individual mice for eachgenotype, and the figure refers to one representative analysis.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC2664975&req=5

fig1: Ablation of L1 in DCs fromTie2-Cre;L1floxed mice. (A)CD11c-positive cells from the lymph nodes of C57BL/6 mice (left) weregated and analyzed for L1 expression (right). Background staining wasdetermined with a control isotype-matched antibody (black line). Theexperiment was repeated with lymph nodes from five individual mice withsimilar results, and the figure refers to one representative analysis ofone mouse. (B) FACS analysis of CD11c and L1 coexpression in bonemarrow–derived DCs from L1floxedand Tie2-Cre;L1floxed mice. The experimentwas repeated with similar results on four individual mice for eachgenotype, and the figure refers to one representative analysis.

Mentions: L1 has been detected in human DCs (5). Toinvestigate whether mouse DCs also express L1, we collected lymph node cellsfrom C57BL/6 mice and determined L1 expression in CD11c+cells. Approximately 55% of DCs were found to be positive for L1 (Fig. 1 A). The analysis of DCsubpopulations showed L1 expression in 45% of CD4+, 40% ofCD8+, and 40% of B220+ DCs, whereas85% Langerhans cells were positive for L1 (Fig. S1 A). Similar results wereobtained in DCs isolated from the spleen (Fig. S1 B). The widespread expressionof L1 in Langerhans cells was also confirmed in the epidermis (see fourthparagraph).


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

Maddaluno L, Verbrugge SE, Martinoli C, Matteoli G, Chiavelli A, Zeng Y, Williams ED, Rescigno M, Cavallaro U - J. Exp. Med. (2009)

Ablation of L1 in DCs fromTie2-Cre;L1floxed mice. (A)CD11c-positive cells from the lymph nodes of C57BL/6 mice (left) weregated and analyzed for L1 expression (right). Background staining wasdetermined with a control isotype-matched antibody (black line). Theexperiment was repeated with lymph nodes from five individual mice withsimilar results, and the figure refers to one representative analysis ofone mouse. (B) FACS analysis of CD11c and L1 coexpression in bonemarrow–derived DCs from L1floxedand Tie2-Cre;L1floxed mice. The experimentwas repeated with similar results on four individual mice for eachgenotype, and the figure refers to one representative analysis.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2664975&req=5

fig1: Ablation of L1 in DCs fromTie2-Cre;L1floxed mice. (A)CD11c-positive cells from the lymph nodes of C57BL/6 mice (left) weregated and analyzed for L1 expression (right). Background staining wasdetermined with a control isotype-matched antibody (black line). Theexperiment was repeated with lymph nodes from five individual mice withsimilar results, and the figure refers to one representative analysis ofone mouse. (B) FACS analysis of CD11c and L1 coexpression in bonemarrow–derived DCs from L1floxedand Tie2-Cre;L1floxed mice. The experimentwas repeated with similar results on four individual mice for eachgenotype, and the figure refers to one representative analysis.
Mentions: L1 has been detected in human DCs (5). Toinvestigate whether mouse DCs also express L1, we collected lymph node cellsfrom C57BL/6 mice and determined L1 expression in CD11c+cells. Approximately 55% of DCs were found to be positive for L1 (Fig. 1 A). The analysis of DCsubpopulations showed L1 expression in 45% of CD4+, 40% ofCD8+, and 40% of B220+ DCs, whereas85% Langerhans cells were positive for L1 (Fig. S1 A). Similar results wereobtained in DCs isolated from the spleen (Fig. S1 B). The widespread expressionof L1 in Langerhans cells was also confirmed in the epidermis (see fourthparagraph).

Bottom Line: 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.Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs.

View Article: PubMed Central - PubMed

Affiliation: The FIRC Institute of Molecular Oncology, 20139 Milan, Italy.

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.

Show MeSH
Related in: MedlinePlus