A combination of MIP-3alpha and TGF-beta1 is required for the attraction of human Langerhans precursor cells through a dermal-epidermal barrier.
Signals regulating the traffic of Langerhans cell precursors from blood to the epidermis are not yet fully understood. The observations that TGF-beta1 is of unique importance in Langerhans cells (LC) ontogeny and that macrophage inflammatory protein-3alpha (MIP-3alpha) is able to attract LC within the epidermis, prompted us to study the effect of MIP-3alpha and TGF-beta1 on the migration of LC precursors. The migratory capacity of immature dendritic cells (DC) was assessed using a reconstituted basement membrane assay (Matrigel), mimicking the prerequisite passage through the dermal-epidermal basement membrane on the way into the epidermis. DC differentiated from cord blood CD34 cells in the presence of GM-CSF plus TNF-alpha were subjected to migration using modified Boyden chambers. Day-6 DC progenitors migrated in a dose-dependent fashion in response to MIP-3alpha, and CD1alpha+ LC precursors responded preferentially to the chemokine. Immature DC did not respond strongly to TGF-beta1 alone in migration assays, but up to 68% of the cells migrated in response to MIP-3alpha plus TGF-beta1. Among them, at least 50% expressed CD1a and E-cadherin and can be considered LC precursors. The allostimulatory function of these cells was significantly more potent than that which migrated in response to MIP-3alpha alone. Our results show that a significant proportion of immature DC is able to migrate through a dermal-epidermal basement membrane equivalent. In the presence of TGF-beta1, the DC which respond to MIP-3alpha have the phenotype and the functional capacity of epidermal LC. Our findings underline the role of MIP-3alpha and TGF-beta1 in attraction and localization of immature LC within the epidermis under normal conditions.
Godefroy
S
S
INSERM U346, CNRS, Department of Dermatology, E.Herriot Hospital, Lyon/France.
Guironnet
G
G
Jacquet
C
C
Schmitt
D
D
Staquet
M J
MJ
D001485:Basement Membrane / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000494:pharmacology*; D000078404:Epidermal Cells; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology* / Q000187:drug effects; D008213:Lymphocyte Activation / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1