Plasmacytoid dendritic cells employ multiple cell adhesion molecules sequentially to interact with high endothelial venule cells - molecular basis of their trafficking to lymph nodes

Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
International Immunology (Impact Factor: 2.54). 10/2007; 19(9):1031-7. DOI: 10.1093/intimm/dxm088
Source: PubMed


Plasmacytoid dendritic cells (pDCs) are natural type I IFN-producing cells found in lymphoid tissues, where they support both innate and adaptive immune responses. They emigrate from the blood to lymph nodes, apparently through high endothelial venules (HEVs), but little is known about the mechanism. We have investigated the molecular mechanisms of pDC migration using freshly isolated DCs and HEV cells. We found that pDCs bound avidly to HEV cells and then transmigrated underneath them. Two observations suggested that these binding and migration steps are differentially regulated. First, treatment of pDCs with pertussis toxin blocked transmigration but not binding. Second, pDCs were able to bind but not to transmigrate under non-HEV endothelial cells, although the binding was observed to both HEV and non-HEV endothelial cells. Antibody inhibition studies indicated that the binding process was mediated by alphaL and alpha4 integrins on pDCs and by intercellular adhesion molecule (ICAM)-1, ICAM-2 and vascular cell adhesion molecule-1 on HEVs. The transmigration process was also mediated by alphaL and alpha4 integrins on pDCs, with junctional adhesion molecule-A on HEV cells apparently serving as an additional ligand for alphaL integrin. These data show for the first time that pDCs employ multiple adhesion molecules sequentially in the processes of adhesion to and transmigration through HEVs.

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Available from: Toshiyuki Tanaka
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    • "Regarding migration to lymph tissue, it is interesting to note that trafficking is directed to LNs that drain sites of inflammation [49] and that the path they travel differs from the one used by cDCs. In contrast to resting cDCs, which reside in tissues and migrate to the T cell area of local lymph nodes via the afferent lymphatics [31], pDCs migrate via the high endothelial venules (HEV) [50] involving L-selectin and CCR7 [49] [51]. The mechanism of trafficking into the tissue remains less well defined, but may involve CXCR3, the receptor for IP-10 and two other related, interferon-induced chemokines, I-TAC and MIG. "
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