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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Increased CHS response in Jam-A –/– mice. (A) Animals were sensitized wi...
Increased CHS response in Jam-A –/– mice. (A) Animals were sensitized with OXA on their shaved abdominal skin and 5 days later were challenged on the right ear. Ear swelling was measured and expressed as percent increase over controls (left ear was painted with vehicle alone). The control mean values ± SEM were comparable: 23.86 × 10–2 ± 0.46 × 10–2 mm for Jam-A+/+ mice and 23.50 × 10–2 ± 0.28 × 10–2 mm for Jam-A –/– mice. The values reported in the figure are mean ± SEM (8 mice per group) of one representative experiment out of three performed (*P ≤ 0.05 and **P < 0.01 by Student’s t test). (B) Jam-A+/+ mice were immunized by subcutaneous injection of DNBS-loaded DCs obtained from Jam-A+/+ or Jam-A –/– mice (see Methods). Mice were challenged 5 days later by ear painting with DNFB. Figures represent the percent increase of ear swelling over controls. Mean values ± SEM (8 mice per group) of one representative experiment out of three performed are shown (*P ≤ 0.05 and **P < 0.01 by Student’s t test). Mean ± SEM of vehicle-treated ears was comparable between both groups (22.63 × 10–2 ± 0.26 × 10–2 mm for Jam-A+/+ and 22.25 × 10–2 ± 0.16 × 10–2 mm for Jam-A –/– mice).