TY - JOUR
T1 - Molecular characterization of human skin response to diphencyprone at peak and resolution phases
T2 - Therapeutic insights
AU - Gulati, Nicholas
AU - Suárez-Fariñas, Mayte
AU - Fuentes-Duculan, Judilyn
AU - Gilleaudeau, Patricia
AU - Sullivan-Whalen, Mary
AU - Correa Da Rosa, Joel
AU - Cueto, Inna
AU - Mitsui, Hiroshi
AU - Krueger, James G.
N1 - Funding Information:
We thank John A Carucci, Emma Guttman-Yassky, and Michelle A Lowes for helpful comments and discussions on this manuscript. This research was supported by National Institutes of Health (NIH) grant UL1 RR024143 from the National Center for Research Resources and the Milstein Medical Program. NG was supported by a Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the NIH under award number T32GM07739 to the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84922393839
U2 - 10.1038/jid.2014.196
DO - 10.1038/jid.2014.196
M3 - Article
C2 - 24751728
AN - SCOPUS:84922393839
SN - 0022-202X
VL - 134
SP - 2531
EP - 2540
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 10
ER -