The lymphoid chemokine CCL21 triggers LFA-1 adhesive properties on human dendritic cells.
Dendritic cells (DCs) are the most potent APCs, involved in the induction of immunity and tolerance. Recently we showed that during differentiation of human DCs from monocyte precursors, Lymphocyte function-associated antigen-1 (LFA-1)-binding capacity is lost, although integrin expression levels were maintained constant, suggesting a different regulation mechanism of this integrin on different cell types. However, the exact role of LFA-1 in DC adhesion and migration remains obscure. Chemokines are potent regulators of integrin function, influencing migratory and adhesive properties of leukocytes. Here, we show that upon vaccination of cancer patients with human DCs, cells that have migrated in vivo into the lymph nodes upregulated the active form of LFA-1. We further show that exposure of human DCs to the lymphoid chemokine CCL21 specifically restores the high-affinity form of LFA-1 and induces binding to its ligand ICAM-1 under low shear stress. Our data indicate that on DCs LFA-1 may function as an inducible anchor during lymphatic transmigration or within the lymph nodes. A thorough understanding of the adhesive events during the DC life cycle will help to improve the outcome of DC-based antitumor clinical trials.
Eich
Christina
C
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
de Vries
I Jolanda M
IJ
Linssen
Peter C M
PC
de Boer
Annemiek
A
Boezeman
Jan B
JB
Figdor
Carl G
CG
Cambi
Alessandra
A
D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054421:Chemokine CCL21 / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology
D054421:Chemokine CCL21; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1