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 1

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Characterization of Jam-A –/– and endothelial Jam-A –/– mice. (A) The ta...
Characterization of Jam-A –/– and endothelial Jam-A –/– mice. (A) The targeted allele containing 3 LoxP sites (flox/flox), the excised allele (Jam-A –/–), and the WT allele (Jam-A+/+) are shown. (B) Genomic PCR of murine tail biopsies. To identify Jam-A –/– mice obtained from interbreeding of heterozygous mice, the combination of CAG–Cre-F, CAG–Cre-R, TS379, TS512, TS447, and TS444 LoxP primers was used. To identify endothelial Jam-A –/– mice, the combination of Tie-2 Cre, TS379, and TS512 primers was used. TS379 and TS512 generate a 500-bp product for minus allele, an 800-bp product for WT allele, and a 3,000-bp product (absence of band) for flox allele. (C) FACS analysis of JAM-A on mouse leukocytes isolated from peritoneal cavities 24 hours after injection of thioglycollate. (D) Expression of JAM-A on endothelial cells derived from lungs of Jam-A+/+ and Jam-A –/– animals evaluated by FACS, immunoprecipitation, and Western blot analysis with mAb BV12. In C and D, gray lines represent negative controls obtained using the secondary Ab alone.