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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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).