Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A–deficient mice
Maria Rosaria Cera, … , Alberto Mantovani, Elisabetta Dejana
Maria Rosaria Cera, … , Alberto Mantovani, Elisabetta Dejana
Published September 1, 2004
Citation Information: J Clin Invest. 2004;114(5):729-738. https://doi.org/10.1172/JCI21231.
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Article Vascular biology

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.

Authors

Maria 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

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Figure 5

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JAM-A expression and in vitro DC migration. (A) Chemotaxis of iDCs and m...
JAM-A expression and in vitro DC migration. (A) Chemotaxis of iDCs and mDCs was evaluated using the Transwell system. Data are presented as percent migration, calculated as described in Methods. Data are mean ± SEM of triplicates from a typical experiment out of three performed. (B) Basal transmigration of Jam-A+/+ and Jam-A –/– mDCs across monolayers of vascular (1G11 cells) or lymphatic (MELCs) endothelial cells grown on the upper or lower side (reversed MELCs) of the filter (see Methods). Data, presented as percent transmigration, are mean ± SEM of triplicates from a typical experiment out of three performed. *P < 0.01 by paired Student’s t test comparing transmigration of Jam-A+/+ and Jam-A –/– mDCs through MELCs. (C) Distribution of particle-free areas in random migration. Each bar represents the percentage of cells that have migrated over the indicated particle area in one representative experiment out of three performed. In this experiment the mean ± SEM of the particle area covered by migrating cells was 378 ± 46 μm2 for Jam-A+/+ iDCs (n = 25 cells), 1,511 ± 249 μm2 for Jam-A –/– iDCs (n = 20 cells), 541 ± 79 μm2 for Jam-A+/+ mDCs (n = 17 cells), and 1,448 ± 217 μm2 for Jam-A –/– mDCs (n = 14 cells).