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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Histological analysis of Jam-A –/– and endothelial Jam-A –/– mice. (A) I...
Histological analysis of Jam-A –/– and endothelial Jam-A –/– mice. (A) Immunofluorescence staining of serial cryosections of Jam-A+/+, Jam-A –/–, and endothelial Jam-A –/– (Tie-2 Cre Jam-A –/–) kidneys using anti-PECAM and anti–JAM-A (BV12) Ab’s. All sections show positive staining for PECAM (both controls and mutants), while JAM-A staining is undetectable in all type of tissues in Jam-A –/– mice. Note that endothelial cells from Tie-2 Cre Jam-A –/– animals are negative for JAM-A staining (arrow). The arrowheads indicate that JAM-A staining on the epithelium of the tubuli is still detectable. Staining is weaker compared with Jam-A+/+ mice since the peritubular capillaries are negative. Scale bar: 200 μm. (B) Immunostaining of serial cryosections of aorta from Jam-A+/+ and Tie-2 Cre Jam-A –/– mice, using anti-PECAM and anti–JAM-A (BV12) Ab’s. Vascular endothelial JAM-A is undetectable in Tie-2 Cre Jam-A –/– aorta. Scale bar: 200 μm. (C) Cryosections of Jam-A+/+ and Tie-2 Cre Jam-A –/– lymph nodes were double stained for LYVE (in green), a marker of lymphatic endothelial cells, and for JAM-A (in red). In Jam-A+/+ mice, the colocalization of JAM-A and LYVE is evident; this was not observed in Tie-2 Cre Jam-A –/– animals. Scale bar: 50 μm.