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Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice.

Abstract
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.
AuthorsMaria Rosaria Cera, Annalisa Del Prete, Annunciata Vecchi, Monica Corada, Ines Martin-Padura, Toshiyuki Motoike, Paolo Tonetti, Gianfranco Bazzoni, William Vermi, Francesca Gentili, Sergio Bernasconi, Thomas N Sato, Alberto Mantovani, Elisabetta Dejana
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 114 Issue 5 Pg. 729-38 (Sep 2004) ISSN: 0021-9738 [Print] United States
PMID15343392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Adhesion Molecules
  • Junctional Adhesion Molecules
Topics
  • Animals
  • Cell Adhesion Molecules (deficiency, genetics, immunology)
  • Cell Movement (genetics, immunology)
  • Dendritic Cells (immunology)
  • Dermatitis, Contact (genetics, immunology)
  • Endothelial Cells
  • Fluorescent Antibody Technique
  • Junctional Adhesion Molecules
  • Lymph Nodes (immunology)
  • Mice
  • Mice, Knockout

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