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