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 | Nicholas Gulati, Mayte Suárez-Fariñas, Judilyn Fuentes-Duculan, Patricia Gilleaudeau, Mary Sullivan-Whalen, Joel Correa da Rosa, Inna Cueto, Hiroshi Mitsui, James G Krueger |
Journal | The Journal of investigative dermatology
(J Invest Dermatol)
Vol. 134
Issue 10
Pg. 2531-2540
(Oct 2014)
ISSN: 1523-1747 [Electronic] United States |
PMID | 24751728
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- Cyclopropanes
- Cytokines
- Haptens
- IDO1 protein, human
- Immunologic Factors
- Indoleamine-Pyrrole 2,3,-Dioxygenase
- diphenylcyclopropenone
|
Topics |
- 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, pathology)
- Male
- Middle Aged
- Skin
(drug effects, metabolism, pathology)
- T-Lymphocytes
(drug effects, pathology)
|