title: Molecular characterization of human skin response to diphencyprone at peak and resolution phases: therapeutic insights.
abstract: Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. It is used as an immune-modulating therapeutic, but its molecular effects in human skin are largely unknown. We studied cellular and molecular characteristics of a recall response to 0.04% DPCP at 3-day (peak) and 14-day (resolution) time points using immune markers, reverse-transcriptase-PCR (RT-PCR), and gene array approaches. A peak response showed modulation of ∼7,500 mRNA transcripts, with high expression of cytokines that define all major effector T-cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC) infiltrates were measured. The resolution reaction was characterized by unexpectedly high levels of T cells and mature (DC-lysosome-associated membrane glycoprotein positive (DC-LAMP+)) DCs, but with marked decreases in expression of IL-2, IFNγ, and other T cell-derived cytokines. However, negative immune regulators such as IDO1 that were high in peak reactions, continued to have high expression in resolution reactions. In the resolution reaction, ∼1,500 mRNA transcripts were significantly different from placebo-treated skin. These data suggest that the response to DPCP evolves from an inflammatory/effector peak at day 3 to a more regulated immune response after 14 days. This model system could be useful for further dissection of mechanisms of immune activation or negative immune regulation in human skin.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA; The Center for Clinical and Translational Science, The Rockefeller University, New York, New York, USA.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.affiliation: The Center for Clinical and Translational Science, The Rockefeller University, New York, New York, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Correa da Rosa
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Cueto
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA. Electronic address: kruegej@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000328:Adult; D001706:Biopsy; D003521:Cyclopropanes / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006241:Haptens / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007801:Langerhans Cells / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
chemical_list: D003521:Cyclopropanes; D016207:Cytokines; D006241:Haptens; C576710:IDO1 protein, human; D007155:Immunologic Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C029402:diphenylcyclopropenone
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