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Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
Dendritic cells (DCs) are the most potent APCs of the immune system that seed the peripheral tissues and lymphoid organs. In an immature state, DCs sample their surroundings for incoming pathogens. Upon Ag encounter, DCs mature and migrate to the lymph node to induce adaptive immune responses. The C-type macrophage galactose-type lectin (MGL), expressed in immature DCs, mediates binding to glycoproteins carrying GalNAc moieties. In the present study, we demonstrate that MGL ligands are present on the sinusoidal and lymphatic endothelium of lymph node and thymus, respectively. MGL binding strongly correlated with the expression of the preferred MGL ligand,
-GalNAc-containing glycan structures, as visualized by staining with the
-GalNAc-specific snail lectin Helix pomatia agglutinin. MGL+ cells were localized in close proximity of the endothelial structures that express the MGL ligand. Strikingly, instead of inducing migration, MGL mediated retention of human immature DCs, as blockade of MGL interactions enhanced DC trafficking and migration. Thus, MGL+ DCs are hampered in their migratory responses and only upon maturation, when MGL expression is abolished; these DCs will be released from their MGL-mediated restraints.
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1 This work was supported by an Netherlands Organization for Scientific Research Pionier Grant 900-02-002.
2 S.J.v.V. and L.C.P. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Yvette van Kooyk, Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, PO Box 7057, 1007MB Amsterdam, The Netherlands. E-mail address: y.vankooyk{at}vumc.nl
4 Abbreviations used in this paper: DC, dendritic cell; HPA, Helix pomatia agglutinin; LN, lymph node; MAA, Maackia amurensis agglutinin; MGL, macrophage galactose-type lectin; SNA, Sambucus nigra agglutinin; PAA, Polyacrylamide.
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