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 DCs from Jam-A+/+ and Jam-A –/– mice. CD34+ bone mar...
Characterization of DCs from Jam-A+/+ and Jam-A –/– mice. CD34+ bone marrow precursor cells were used to generate iDCs and mDCs in vitro, and these were functionally characterized as detailed in Methods. (A) JAM-A expression on Jam-A+/+ and Jam-A –/– iDCs and mDCs. Unlabeled lines correspond to staining with an irrelevant mAb of an identical isotype. (B) Membrane phenotype of iDCs and mDCs from Jam-A+/+ and Jam-A –/– mice. Percentage and mean fluorescence intensity (MFI) of positive cells are shown. (C) Mixed lymphocyte response performed in the presence of different numbers of mDCs from Jam-A+/+ and Jam-A –/– mice. mDCs are most effective in mixed lymphocyte response, and for simplicity only data with mDCs are shown in the Figure. iDCs from Jam-A+/+ and Jam-A –/– mice did not differ in inducing mixed lymphocyte response (data not shown). (D) Uptake of FITC-dextran as evaluated by FACS analysis. Data in B are of one representative experiment out of five performed. Data in C and D are mean ± SEM of one representative experiment out of three performed in triplicate.