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.

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

“…The precise mechanisms of JAM-mediated immune cell diapedesis across the endothelium remains to be defined, as all JAM can undergo homophilic but also heterophilic interactions with leukocyte integrins. Nevertheless, there is evidence for a contribution of JAM-A in HEV to lymphocyte homing to PLN, as this process is slightly impaired in endothelialrestricted JAM-A-deficient mice [28]. JAM-B and JAM-C interact with each other and can form additional interactions with a4b1-integrin and Mac-1, respectively.…”

Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1

“…Male wild-type (WT), C57BL/6, FVB/n, and SJL mice were used, as well as male ICAM-2 Ϫ/Ϫ , 12 JAM-A Ϫ/Ϫ , 16 PECAM-1 Ϫ/Ϫ , 17 and TNF-␣R p55/p75 double knockout (TNFR Ϫ/Ϫ ) mice. All genetically modified mice were on a C57BL/6 background ("Animals" in supplemental materials and methods, available on the Blood website; see the Supplemental Materials link at the top of the online article).…”

Visualizing dendritic cell migration within the skin

“…Jam-A ¡/¡ DCs showed an increase in random motility and in the capacity to transmigrate across lymphatic endothelial cells (Cera et al 2004), possibly through reduced interactions with L 2 integrins (Ostermann et al 2002). Van et al (2006) recently reported a requirement for DC expression of CD47 for successful homing, although the mechanism remains unknown.…”