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International Immunology Advance Access originally published online on September 5, 2007
International Immunology 2007 19(9):1031-1037; doi:10.1093/intimm/dxm088
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© The Author 2007. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
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Plasmacytoid dendritic cells employ multiple cell adhesion molecules sequentially to interact with high endothelial venule cells – molecular basis of their trafficking to lymph nodes

Takahiro Matsutani1,2,*, Toshiyuki Tanaka1,3,*, Kazuo Tohya4, Kazuhiro Otani1,2, Myoung Ho Jang1, Eiji Umemoto1, Kanako Taniguchi1, Haruko Hayasaka1, Koichi Ueda2 and Masayuki Miyasaka1

1 Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan
2 Department of Plastic and Reconstructive Surgery, The Postgraduate Course of Osaka Medical College, Takatsuki, 569-8686, Japan
3 Department of Pharmacy, Laboratory of Immunobiology, School of Pharmacy, Hyogo University of Health Sciences, Kobe, 650-8530, Japan
4 Department of Anatomy, Kansai College of Oriental Medicine, Sennan, 590-0482, Japan

Correspondence to: M. Miyasaka; E-mail: mmiyasak{at}orgctl.med.osaka-u.ac.jp

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 {alpha}L and {alpha}4 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 {alpha}L and {alpha}4 integrins on pDCs, with junctional adhesion molecule-A on HEV cells apparently serving as an additional ligand for {alpha}L 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.

Keywords: adhesion molecules, cell trafficking, high endothelial venule cells, plasmacytoid dendritic cells, transmigration

* These authors contributed equally to this work.

Received 24 May 2007, accepted 27 June 2007.


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