Long-lived immature dendritic cells mediated by TRANCE-RANK interaction.
Immature dendritic cells (DCs) reside in interstitial tissues (int-DC) or in the epidermis, where they capture antigen and, thereafter, mature and migrate to draining lymph nodes (LNs), where they present processed antigen to T cells. We have identified int-DCs that express both TRANCE (tumor necrosis factor-related activation-induced cytokine) and RANK (receptor activator of NF-kappaB) and have generated these cells from CD34(+) human progenitor cells using macrophage colony-stimulating factor (M-CSF). These CD34(+)-derived int-DCs, which are related to macrophages, are long-lived, but addition of soluble RANK leads to significant reduction of cell viability and Bcl-2 expression. This suggests that constitutive TRANCE-RANK interaction is responsible for CD34(+)-derived int-DC longevity. Conversely, CD1a(+) DCs express only RANK and are short-lived. However, they can be rescued from cell death either by recombinant soluble TRANCE or by CD34(+)-derived int-DCs. CD34(+)-derived int-DCs mature in response to lipopolysaccharide (LPS) plus CD40 ligand (L) and become capable of CCL21/CCL19-mediated chemotaxis and naive T-cell activation. Upon maturation, they lose TRANCE, making them, like CD1a(+) DCs, dependent on exogenous TRANCE for survival. These findings provide evidence that TRANCE and RANK play important roles in the homeostasis of DCs.
Cremer
Isabelle
I
Institut National de la Santé et de la Recherche Médicale (INSERM) U255, Centre de Recherches Biomédicales des Cordeliers, and Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
Dieu-Nosjean
Marie-Caroline
MC
Maréchal
Sylvie
S
Dezutter-Dambuyant
Colette
C
Goddard
Sarah
S
Adams
David
D
Winter
Nathalie
N
Menetrier-Caux
Christine
C
Sautès-Fridman
Catherine
C
Fridman
Wolf H
WH
Mueller
Chris G F
CG
D023201:CD40 Ligand / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D053244:Osteoprotegerin; D011485:Protein Binding / Q000276:immunology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D012867:Skin / Q000166:cytology
D002352:Carrier Proteins; D006023:Glycoproteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D023201:CD40 Ligand