Increased DC Trafficking to Lymph Nodes and Contact Hypersensitivity in Junctional Adhesion molecule-A-deficient Mice

J Clin Invest. 2004 Sep;114(5):729-38. doi: 10.1172/JCI21231.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / deficiency*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Dendritic Cells / immunology*
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology*
  • Endothelial Cells
  • Fluorescent Antibody Technique
  • Junctional Adhesion Molecules
  • Lymph Nodes / immunology*
  • Mice
  • Mice, Knockout

Substances

  • Cell Adhesion Molecules
  • Junctional Adhesion Molecules