Long-lived immature dendritic cells mediated by TRANCE-RANK interaction

Blood. 2002 Nov 15;100(10):3646-55. doi: 10.1182/blood-2002-01-0312. Epub 2002 Jul 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD40 Ligand / pharmacology
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Lineage
  • Cell Movement
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Glycoproteins / pharmacology*
  • Humans
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Culture Test, Mixed
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / pharmacology*
  • Osteoprotegerin
  • Protein Binding / immunology
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / immunology
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Tumor Necrosis Factor
  • Skin / cytology

Substances

  • Carrier Proteins
  • Glycoproteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • CD40 Ligand