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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-01-0312.
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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3646-3655
IMMUNOBIOLOGY
Long-lived immature dendritic cells mediated by TRANCE-RANK
interaction
Isabelle Cremer,
Marie-Caroline Dieu-Nosjean,
Sylvie Maréchal,
Colette Dezutter-Dambuyant,
Sarah Goddard,
David Adams,
Nathalie Winter,
Christine Menetrier-Caux,
Catherine Sautès-Fridman,
Wolf H. Fridman, and
Chris G. F. Mueller
From the 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; INSERM U346, Hôpital Edouard Herriot, and INSERM U453,
Centre Léon Bérard, Lyon, France; and Liver Unit
Laboratories, Queen Elizabeth Hospital, Birmingham, Great
Britain.
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- B) 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.
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