Epidermal receptor activator of NF-kappaB ligand controls Langerhans cells numbers and proliferation.
Langerhans cells (LC) are the dendritic APC population of the epidermis, where they reside for long periods and are self-replicating. The molecular signals underlying these characteristics are unknown. The TNF superfamily member receptor activator of NF-kappaB ligand (RANKL, TNFSF11) has been shown to sustain viability of blood dendritic cells in addition to its role in promoting proliferation and differentiation of several cell types, notably osteoclasts. In this study, we have studied expression of the RANKL system in skin and have defined a key role for this molecule in LC homeostasis. In vitro and in vivo, human KC expressed RANKL and epidermal LC expressed cell surface RANK. In vitro, RANKL sustained CD34(+) progenitor-derived LC viability following 72-h cultures in cytokine-free medium (79.5 +/- 1% vs 55.2 +/- 5.7% live cells, respectively; n = 4; p < 0.05). In vivo, RANKL-deficient mice displayed a marked reduction in epidermal LC density (507.1 +/- 77.2 vs 873.6 +/- 41.6 LC per mm(2); n = 9; p < 0.05) and their proliferation was impaired without a detectable effect on apoptosis. These data indicate a key role for the RANKL system in the regulation of LC survival within the skin and suggest a regulatory role for KC in the maintenance of epidermal LC homeostasis.
Barbaroux
Jean-Baptiste O
JB
St John's Institute of Dermatology, King's College London, London, United Kingdom. jean-baptiste.barbaroux@kcl.ac.uk
Beleut
Manfred
M
Brisken
Cathrin
C
Mueller
Christopher G
CG
Groves
Richard W
RW
D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D053245:RANK Ligand / Q000276:immunology / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human