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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Morphology, JAM-A expression, and DC distribution in lymph node and skin...
Morphology, JAM-A expression, and DC distribution in lymph node and skin sections. (A) H&E staining of a lymph node section from a Jam-A –/– mouse displays normal architecture including cortical lymphoid nodules (CN) and an expanded paracortical area (PC); PC is populated by DCs, highlighted by their strong expression of MHC class II molecule (inset). (B) Expression of JAM-A in a lymph node section from a Jam-A+/+ mouse is evident in sinus macrophages (asterisk), high endothelial venules (arrowheads in B and C), and DCs in the paracortex (C, black arrow). (D) In normal skin, a diffuse JAM-A expression is observed in epidermal and pilar keratinocytes, in endothelial cells of dermal vessels (arrowhead), and in scattered fusate/stellate dermal cells (inset). (E) A skin section from a Jam-A –/– mouse illustrates the regular distribution of MHC class II+ LCs; LCs display an evident dendritic morphology with fine and long dendrites, and express Langerin (insert). (F and G) Sections from an inguinal lymph node obtained after FITC skin painting display green-dotted FITC+ cells in the paracortex that coexpress JAM-A (F, arrow) and Langerin (G, arrow). MHC class II+ and JAM-A+ cells were detected by immunoperoxidase technique as seen in A (inset), B, C, and D. Immunofluorescence staining was used to detect JAM-A+ cells (red cells in F), MHC class II+ LCs (red cells in E), and Langerin+ LCs (red cells, inset in E; G). Magnification: ×40 in A, ×200 in F and G, ×400 in B, D, and E, and ×600 in insert in A, C, insert in D, and insert in E. Scale bars: 500 μm in A, 50 μm in B, 20 μm in C, and 100 μm in F.