Differential regulation of epidermal and dermal dendritic cells by IL-12 and Flt3 ligand.
An abrogation of the decline in epidermal Langerhans cell numbers above melanoma might significantly improve the efficacy of immunotherapy for melanoma treatment. Systemic Flt3 ligand (FL) administration in mice induced a significant increase in mature dendritic cells (DC) within the skin, preferentially in the dermis, whereas IL-12 promoted a significant increase of immature DC preferentially in the epidermis. Both effects were abrogated in IL-12 knockout mice. Thus, IL-12 could promote FL-induced accumulation of skin DC. The involvement of FL and IL-12 in the regulation of DC accumulation within the skin may contribute, at least in part, to the stimulation of antimelanoma immunity by FL- and IL-12-based immunotherapies. Moreover, FL and IL-12 could be used for selective in vivo generation of DC in either epidermis or dermis for experimental and clinical purposes.
Esche
C
C
University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
Subbotin
V M
VM
Hunter
O
O
Peron
J M
JM
Maliszewski
C
C
Lotze
M T
MT
Shurin
M R
MR
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects*; D004357:Drug Synergism; D004817:Epidermis / Q000187:drug effects*; D018664:Interleukin-12 / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000187:drug effects*
D008565:Membrane Proteins; C084881:flt3 ligand protein; D018664:Interleukin-12