Plasmacytoid dendritic cell recruitment by immobilized CXCR3 ligands.
Plasmacytoid dendritic cells (pDCs) recognize microbes, viruses in particular, and provide unique means of innate defense against them. The mechanism of pDC tissue recruitment remained enigmatic because the ligands of CXCR3, the cardinal chemokine receptor on pDCs, have failed to induce in vitro chemotaxis of pDCs in the absence of additional chemokines. In this study, we demonstrate that CXCR3 is sufficient to induce pDC migration, however, by a migratory mechanism that amalgamates the features of haptotaxis and chemorepulsion. To mediate "haptorepulsion" of pDCs, CXCR3 requires the encounter of its cognate ligands immobilized, optimally by heparan sulfate, in a form of a negative gradient. This is the first report of the absolute requirement of chemokine immobilization and presentation for its in vitro promigratory activity. The paradigmatic example of pDC haptorepulsion described here may represent a new pathophysiologically relevant migratory mechanism potentially used by other cells in response to other chemokines.
Kohrgruber
Norbert
N
Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Gröger
Marion
M
Meraner
Paul
P
Kriehuber
Ernst
E
Petzelbauer
Peter
P
Brandt
Sabine
S
Stingl
Georg
G
Rot
Antal
A
Maurer
Dieter
D
D017951:Antigen Presentation; D002448:Cell Adhesion / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006497:Heparan Sulfate / Q000276:immunology / Q000378:metabolism; D006562:Herpes Zoster / Q000276:immunology / Q000473:pathology; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008024:Ligands; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000502:physiology*; D018139:Simplexvirus / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D006497:Heparan Sulfate; D016898:Interferon-alpha; D008024:Ligands; D037342:Pertussis Toxin; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014443:Tyrosine; C515370:CCR7 protein, human; C515255:CXCL12 protein, human; C515187:CXCR3 protein, human