Diphencyprone (DPCP) is a
hapten that causes delayed-type
hypersensitivity (DTH) reactions in human skin, and is used as a topical therapeutic for
alopecia areata,
warts, and cutaneous
melanoma metastases. We examined peak DTH reactions induced by DPCP (3 days post-challenge) by comprehensive gene expression and histological analysis. To better understand how these DTH reactions naturally resolve, we compared our DPCP biopsies to those from patients with
psoriasis vulgaris, a chronic inflammatory disease that does not resolve. By both microarray and qRT-PCR, we found that
psoriasis lesional skin has significantly lower expression of many negative immune regulators compared to peak DPCP reactions. These regulators include:
interleukin-10, cytotoxic T lymphocyte-associated 4 (CTLA4), programmed cell death 1 (PD1),
programmed cell death 1 ligand 1 (PDL1), programmed cell death 1
ligand 2 (PDL2), and
indoleamine 2,3-dioxygenase (IDO1). Their decreased expression was confirmed at the
protein level by immunohistochemistry. To more completely determine the balance of positive vs. negative immune regulators in both DPCP reactions and
psoriasis, we developed one comprehensive gene list for positive regulatory (inflammatory) genes, and another for negative regulatory (immunosuppressive) genes, through Gene Ontology terms and literature review. With this approach, we found that DPCP reactions have a higher ratio of negative to positive regulatory genes (both in terms of quantity and expression levels) than
psoriasis lesional skin. These data suggest that the disease chronicity that distinguishes
psoriasis from transient DTH reactions may be related to absence of negative immune regulatory pathways, and induction of these is therefore of therapeutic interest. Further study of these negative regulatory mechanisms that are present in DPCP reactions, but not in
psoriasis, could reveal novel players in the pathogenesis of chronic
inflammation. The DPCP system used here thus provides a tractable model for primary discovery of pathways potentially involved in immune regulation in peripheral tissues.