title: Differential regulation of epidermal and dermal dendritic cells by IL-12 and Flt3 ligand.
abstract: 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.
authors.affiliation: University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
authors.forename: C
authors.initials: C
authors.lastname: Esche
authors.forename: V M
authors.initials: VM
authors.lastname: Subbotin
authors.forename: O
authors.initials: O
authors.lastname: Hunter
authors.forename: J M
authors.initials: JM
authors.lastname: Peron
authors.forename: C
authors.initials: C
authors.lastname: Maliszewski
authors.forename: M T
authors.initials: MT
authors.lastname: Lotze
authors.forename: M R
authors.initials: MR
authors.lastname: Shurin
mesh_terms: 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*
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein; D018664:Interleukin-12