Molecular characterization of human skin response to diphencyprone at peak and resolution phases: therapeutic insights

J Invest Dermatol. 2014 Oct;134(10):2531-2540. doi: 10.1038/jid.2014.196. Epub 2014 Apr 21.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biopsy
  • Cyclopropanes / pharmacology*
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Haptens / pharmacology*
  • Humans
  • Immunity, Cellular / drug effects
  • Immunologic Factors / pharmacology*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Langerhans Cells / drug effects
  • Langerhans Cells / pathology
  • Male
  • Middle Aged
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology

Substances

  • Cyclopropanes
  • Cytokines
  • Haptens
  • Immunologic Factors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • indoleamine 2,3-dioxygenase 1, human
  • diphenylcyclopropenone