Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice.
Junctional adhesion molecule-A (JAM-A) is a transmembrane adhesive protein expressed at endothelial junctions and in leukocytes. In the present work, we found that DCs also express JAM-A. To evaluate the biological relevance of this observation, Jam-A(-/-) mice were generated and the functional behavior of DCs in vitro and in vivo was studied. In vitro, Jam-A(-/-) DCs showed a selective increase in random motility and in the capacity to transmigrate across lymphatic endothelial cells. In vivo, Jam-A(-/-) mice showed enhanced DC migration to lymph nodes, which was not observed in mice with endothelium-restricted deficiency of the protein. Furthermore, increased DC migration to lymph nodes was associated with enhanced contact hypersensitivity (CHS). Adoptive transfer experiments showed that JAM-A-deficient DCs elicited increased CHS in Jam-A(+/+) mice, further supporting the concept of a DC-specific effect. Thus, we identified here a novel, non-redundant role of JAM-A in controlling DC motility, trafficking to lymph nodes, and activation of specific immunity.
Cera
Maria Rosaria
MR
Department of Vascular Biology, Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology, Milan, Italy.
Del Prete
Annalisa
A
Vecchi
Annunciata
A
Corada
Monica
M
Martin-Padura
Ines
I
Motoike
Toshiyuki
T
Tonetti
Paolo
P
Bazzoni
Gianfranco
G
Vermi
William
W
Gentili
Francesca
F
Bernasconi
Sergio
S
Sato
Thomas N
TN
Mantovani
Alberto
A
Dejana
Elisabetta
E
D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology*; D042783:Endothelial Cells; D005455:Fluorescent Antibody Technique; D062726:Junctional Adhesion Molecules; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules