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DC-SIGN–ICAM-2 interaction mediates dendritic cell trafficking

Abstract

Dendritic cells (DCs) are recruited from blood into tissues to patrol for foreign antigens. After antigen uptake and processing, DCs migrate to the secondary lymphoid organs to initiate immune responses. We now show that DC-SIGN, a DC-specific C-type lectin, supports tethering and rolling of DC-SIGN–positive cells on the vascular ligand ICAM-2 under shear flow, a prerequisite for emigration from blood. The DC-SIGN–ICAM-2 interaction regulates chemokine-induced transmigration of DCs across both resting and activated endothelium. Thus, DC-SIGN is central to the unusual trafficking capacity of DCs, further supported by the expression of DC-SIGN on precursors in blood and on immature and mature DCs in both peripheral and lymphoid tissues.

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Figure 1: ICAM-2 is an endothelial counterstructure for DC-SIGN.
Figure 2: DC-SIGN has a higher affinity for ICAM-2 and ICAM-3 than does LFA-1.
Figure 3: DC-SIGN mediates tethering and rolling on ICAM-2 under physiological conditions.
Figure 4: DC-SIGN mediates SDF-1–induced transmigration of DCs across resting and TNF-α–activated endothelium.
Figure 5: Expression of DC-SIGN.

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Acknowledgements

We thank D. Simmons for recombinant ICAM-1–Fc, ICAM-2–Fc and ICAM-3–Fc constructs, J. H. J. M. van Krieken for advice on immunohistochemistry, G. N. Muijen for providing tissue cryosections, G. Vierwinden and A. Pennings for cell sorting, and A. J. Engering and L. Colledge for reading the manuscript. Supported by the Dutch Cancer Society (grant 96-1358), the Netherlands Organization for Scientific Research (grant 901-09-244) and the Netherlands Heart Foundation (grant 96-150).

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Correspondence to Yvette van Kooyk.

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Geijtenbeek, T., Krooshoop, D., Bleijs, D. et al. DC-SIGN–ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol 1, 353–357 (2000). https://doi.org/10.1038/79815

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