Human Skin Reactions Research Articles

Erythematous reactions to two ultraviolet excimer therapy devices with different irradiance levels: Reconsidering the reciprocity law.

Few studies have examined the effectiveness of the reciprocity law in ultraviolet excimer therapy. This study aimed to examine the difference in erythematous reaction in human skin when the irradiance of ultraviolet excimer treatment devices differed while the irradiation dose was constant. This study, conducted at the Department of Dermatology, Chiba University, included 15 healthy adults aged 20-65 years (mean age, 46.3 years; seven men). Using ultraviolet excimer treatment devices with different irradiances (50 or 150mW/cm2 ), the upper abdomen of each participant was irradiated with ultraviolet light at set irradiation doses (80, 100, 120, 140, 160, 180, and 200 mJ/cm2 ). The erythema index of each irradiated site was measured using a melanin- and erythema-measuring device, and the difference in erythema index before and 24h after irradiation was the primary endpoint. The change in erythema index was significantly higher for an irradiance of 150mW/cm2 . Significant differences (p<0.05) were observed between these irradiance levels at irradiation doses of 100-200 mJ/cm2 . Even for the same irradiation dose, stronger erythematous reactions occurred at higher irradiances in ultraviolet excimer treatment. This suggests that the reciprocity law may not always hold true in excimer therapy.

Unique protein signatures evolve during the course of a delayed-type hypersensitivity reaction in human skin.

Diphencyprone (DPCP) is a hapten that causes a delayed-type hypersensitivity reaction when applied topically. It has clinical uses in the treatment of various conditions such as melanoma metastases, warts, and alopecia areata, but the mechanisms are currently not well understood in humans. To further characterize the immunologic effects of DPCP, the authors performed a proteomic analysis of normal skin of eight healthy volunteers following a single application of DPCP and compared them with placebo-treated skin from the same volunteers. A total of 96 proteins were examined using the Olink immuno-oncology panel at 3 days (peak response), 14 days (partially resolved response), and 120 days (completely resolved response). Our analysis revealed significant upregulation of markers of immune cell activation (interleukin [IL] 8), vascular and tissue remodeling (matrix metallopeptidase 12 [MMP12], nitric oxide synthase 3 [NOS3]), antineoplastic markers (granzyme B [GZMB]), and the Th1 axis (interferon gamma [IFNG], chemokine (C-X-C motif) ligand [CXCL] 9, CXCL10, CXCL11) at days 3 and 14 compared with placebo (p < 0.05). In addition, several negative regulators of immune function such as programmed cell death 1 (PD1), programmed cell death ligand 1 (PDL1) (p < 0.001), and lymphocyte activation gene 3 (LAG3) (p < 0.05) were significantly upregulated at days 3 and 14. This induction of negative regulators may explain the seemingly paradoxical therapeutic benefits of DPCP in autoimmune conditions such as alopecia areata. The current analysis also indicated IL-4 upregulation only at day 3, followed by IL-12 upregulation only at day 14, suggesting a transient Th2 response followed by Th1 polarization. Overall, these data suggest a complex and evolving immunological delayed-type hypersensitivity response to a single application of DPCP over time. Future proteomic studies of samples from patients with melanoma metastases, warts, and alopecia areata treated long term with DPCP are needed to further evaluate its pharmacologic mechanisms.

Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-α Stimulation.

Human skin is constructed with many proteins such as collagen and elastin. Collagen and elastin play a key role in providing strength and elasticity to the human skin and body. However, damage to collagen causes various symptoms such as wrinkles and freckles, which suggests that they are important to maintain skin condition. Extrinsic or intrinsic skin aging produces an excess of skin destructive factors such as tumor necrosis factor (TNF)-α, which is a major mediator of the aging process. In aged skin, TNF-α provokes the generation of intracellular ROS (reactive oxygen species). It triggers the excessive secretion of MMP-1, which is a collagen-degrading enzyme that causes the collapse of skin collagen. Therefore, we aimed to search for a natural-product-derived candidate that inhibits the skin damage caused by TNF-α in human dermal fibroblasts. In this study, the protective effect of withagenin A diglucoside (WAD) identified from Withania somnifera against TNF-α-stimulated human dermal fibroblasts is investigated. W. somnifera (Solanaceae), well-known as 'ashwagandha', is an Ayurvedic medicinal plant useful for promoting health and longevity. Our experimental results reveal that WAD from W. somnifera suppresses the generation of intercellular ROS. Suppressing intracellular ROS generation inhibits MMP-1 secretion and the collapse of type 1 collagen. The effect of WAD is shown to depend on the inhibition of MAPK phosphorylation, Akt phosphorylation, c-Jun phosphorylation, COX-2 expression, and NF-κB phosphorylation. Further, WAD-depressed expression of the pro-inflammatory cytokines IL-6 and IL-8 triggers various inflammatory reactions in human skin. These findings suggest that WAD has protective effects against skin damage. Accordingly, our study provides experimental evidence that WAD can be a potential agent that can be applied in various industrial fields, such as cosmetics and pharmaceuticals related to skin aging.

Efficacy of Diptera-targeted Bacillus thuringiensis var. israelensis against the pine processionary moth, Thaumetopoea wilkinsoni (Lepidoptera: Notodontidae)

The pine processionary moth Thaumetopoea wilkinsoni (Tams, 1926) (Lepidoptera: Notodontidae) is one of the most harmful species that destroys to the pine ecosystem and causes severe skin reactions in humans and animals due to its urticating setae. The aim of this study is to evaluate the efficacy of the hypertoxic strain of Diptera-targeted Bacillus thuringiensis var. israelensis against the second instar larvae of T. wilkinsoni under laboratory conditions. A total of 5 mL of bacterial strain spray was applied to 30 larvae at concentrations of 101, 103, 105, 107, and 109 cfu/mL. As a result of the study, it was determined that the survival rate of the larvae exposed to Bti pHTppk decreased with increasing bacterial concentration, and the survival rate of the 109 cfu/mL concentration group was 33.3%. It is suggested that Bti pHTppk is virulent for T. wilkinsoni larvae and that this strain can be used in the biological control of this species.

036 Unique proteins appear at different times during the course of a delayed-type hypersensitivity reaction in human skin

Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions and is used therapeutically for various conditions including alopecia areata and melanoma metastases. Prior work has shown gene expression markers of major T cell subsets (Th1, Th2, and Th17) are significantly increased at 3 days after a single application of DPCP in healthy volunteers. We evaluated the cutaneous proteome of DPCP reactions in the skin of eight healthy volunteers at days 3, 14, and 120 after application.

Variations in urban forest allergy potential among cities and land uses

Tree pollen with allergenic potential in cities triggers nasal, skin, eye, and asthmatic allergic reactions in humans. Pollen is one of the most common allergy-causing inhaled substances. Tree species composition, cultivar selection and the proximity of certain trees to humans can influence allergic responses. Data from 53 cities or states from various parts of the world were used to assess the magnitude and differences in an allergy index (AI) among the sampled locations and among land uses within cities. Index values for species ranged from one (most allergy-free species) to 10 (highest allergy potential). The average index score among the cities and states was 6.3, with values ranging from 4.2 (Halifax, Nova Scotia) to 8.3 (Austin, Texas). On average, forest/open space areas had a slightly higher average index score (6.4) than commercial/industrial/transportation (6.2) and residential areas (6.1). About 2/3 of the analyzed cities had higher index scores in forest/open space than in residential areas. Forest/open space areas contributed over 40 percent of total leaf area and may influence allergenicity in cities. Cities developed within areas with naturally occurring Pinaceae (pine, spruce, fir, cedar, Douglas fir, larch) forests and/or have more Pinaceae species tended to have the lowest pollen index scores. Most leaf area tended to come from trees in index class 8. While pollen production is essential for natural regeneration and potential seed/food production, limiting tree species with high allergenic potential in areas near people can help reduce tree-related allergies. Through better understanding and quantification of urban forest allergenicity, managers can create sustainable local-scale landscapes that limit pollen exposure to humans, but also provide numerous ecosystem services and values to residents.

A qualitative study on the rejection reaction of human skin to metal

A qualitative study on the rejection reaction of human skin to metal

Assessment of dermal safety of oil extracted from Periplaneta americana: acute dermal toxicity, irritation, and sensitization

Introduction The American cockroach (Periplaneta americana) is used in traditional Chinese medicine. Periplaneta americana (P. americana) is rich in oil that has shown potential antioxidant and antibacterial activities in vitro. Objective To evaluate the safety of oil extracted from P. americana by conducting acute dermal toxicity, irritation, and sensitization tests. Materials and methods In an acute dermal toxicity study, adult Sprague–Dawley rats were exposed to P. americana oil (2000 mg/kg body weight) for 24 h. Clinical observations were conducted to evaluate the toxicity, behaviour, and health of the animals every day after dermal exposure for 14 days. For the dermal irritation test, the oil was applied to rabbits in single and multiple doses. Multi-dose treatment was administered once per day for 14 days. Each rabbit served as its own left- and right-side control and the rabbits’ irritation reactions in local intact and damaged skin were recorded and scored. The skin sensitization study of guinea pigs with the oil was conducted for a period of 28 days. Results The acute dermal median lethal dose (LD50) of P. americana oil was > 2000 mg/kg body weight in adult rats. There was no significant difference in mean irritation scores between the negative control and oil groups. The oil caused very little or no irritation in the intact and damaged skin rabbits treated with either single or multiple doses and it was non-sensitizing to the skin of guinea pigs. Conclusions These results suggest that P. americana oil does not produce any significant acute toxic effects and is safe for use in animal models with almost no dermal irritation or sensitization. Therefore, it presents a low risk of provoking skin reactions in humans.

Complexity-based decoding of brain-skin relation in response to olfactory stimuli

Background and ObjectiveHuman body is covered with skin in different parts. In fact, skin reacts to different changes around human. For instance, when the surrounding temperature changes, human skin will react differently. It is known that the activity of skin is regulated by human brain. In this research, for the first time we investigate the relation between the activities of human skin and brain by mathematical analysis of Galvanic Skin Response (GSR) and Electroencephalography (EEG) signals. MethodFor this purpose, we employ fractal theory and analyze the variations of fractal dimension of GSR and EEG signals when subjects are exposed to different olfactory stimuli in the form of pleasant odors. ResultsBased on the obtained results, the complexity of GSR signal changes with the complexity of EEG signal in case of different stimuli, where by increasing the molecular complexity of olfactory stimuli, the complexity of EEG and GSR signals increases. The results of statistical analysis showed the significant effect of stimulation on variations of complexity of GSR signal. In addition, based on effect size analysis, fourth odor with greatest molecular complexity had the greatest effect on variations of complexity of EEG and GSR signals. ConclusionTherefore, it can be said that human skin reaction changes with the variations in the activity of human brain. The result of analysis in this research can be further used to make a model between the activities of human skin and brain that will enable us to predict skin reaction to different stimuli.

Mast Cells and Sensory Nerves Contribute to Neurogenic Inflammation and Pruritus in Chronic Skin Inflammation.

The intimate interaction between mast cells and sensory nerves can be illustrated by the wheal and surrounding flare in an urticarial reaction in human skin. This reaction is typically associated with an intense itch at the reaction site. Upon activation, cutaneous mast cells release powerful mediators, such as histamine, tryptase, cytokines, and growth factors that can directly stimulate corresponding receptors on itch-mediating sensory nerves. These include, e.g., H1- and H4-receptors, protease-activated receptor-2, IL-31 receptor, and the high-affinity receptor of nerve growth factor (TrkA). On the other hand, sensory nerves can release neuropeptides, including substance P and vasoactive intestinal peptide, that are able to stimulate mast cells to release mediators leading to potentiation of the reciprocal interaction, inflammation, and itch. Even though mast cells are well recognized for their role in allergic skin whealing and urticaria, increasing evidence supports the reciprocal function between mast cells and sensory nerves in neurogenic inflammation in chronic skin diseases, such as psoriasis and atopic dermatitis, which are often characterized by distressing itch, and exacerbated by psychological stress. Increased morphological contacts between mast cells and sensory nerves in the lesional skin in psoriasis and atopic dermatitis as well as experimental models in mice and rats support the essential role for mast cell-sensory nerve communication in consequent pruritus. Therefore, we summarize here the present literature pointing to a close association between mast cells and sensory nerves in pruritic skin diseases as well as review the essential supporting findings on pruritic models in mice and rats.

The dynamics of pigment reactions of human skin to ultraviolet A radiation.

The pigment responses of human skin to broadband UVA radiation (320-400nm) occur in three distinct phases. The first phase includes immediate pigment darkening (IPD), the pigment that appears immediately after irradiation. The second phase involves an intermediate step, termed persistent pigment darkening (PPD), which leads to the third phase of neomelanogenesis or delayed tanning (DT). Since DT results from synthesis of new melanin, it persists beyond 5-7days. We conducted studies on human subjects to investigate the dynamic responses of the IPD and PPD reactions to broadband UVA radiation at threshold and superthreshold doses. The threshold doses for IPD, PPD, and DT were found to be approximately 1, 11, and 18J/cm2 , respectively. The colorimetry ΔL* value corresponding to minimal clinically perceptible pigmentation was found to be 0.8±0.1. IPD appeared immediately and had an associated decay constant of approximately 1.4minutes. At doses greater than PPD threshold, IPD reaction decayed while PPD developed indicating toward IPD being used as a substrate in the formation of PPD.

Pattern analysis of 532- and 1064-nm microlens array-type, picosecond-domain laser-induced tissue reactions in ex vivo human skin.

Optical pulses from picosecond lasers can be delivered to the skin using microlens array (MLA) optics or a diffractive beam splitter to generate multiple, focused, high-intensity, micro-injury zones in the epidermis and dermis. The aim of our study was to histopathologically and immunohistochemically evaluate the patterns of 532- and 1064-nm MLA-type, picosecond laser-induced tissue reactions in human skin immediately after treatment. Picosecond neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment using an MLA-type beam at the wavelengths of 532nm and 1064nm was delivered ex vivo to human skin. Irradiated skin specimens were then microscopically analyzed after hematoxylin and eosin staining and CD31 and Melan-A immunostaining. A single pulse of 532-nm MLA-type, picosecond laser treatment elicited cystic cavitation lesions at sizes of 83.4 ± 16.5μm × 70.2 ± 17.3μm (31-mm distance step) and 91.0 ± 44.7μm × 81.2 ± 36.3μm (48-mm distance step) in the epidermis and papillary dermis. Meanwhile, a single pulse of 1064-nm laser treatment generated cystic cavitation lesions at sizes of 107.0 ± 18.1μm × 83.3 ± 37.4μm (single-pulse mode) and 100.8 ± 40.4μm × 83.1 ± 29.4μm (dual-pulse mode) throughout the lower epidermis and upper papillary dermis. Lining epithelial cells in cystic cavitation lesions in the epidermis showed Melan-A-positive immunoreactivity, while cystic cavitation lesions in the dermis exhibited CD31-positive or CD31-negative/Melan-A-negative immunoreactivity. The present data can be used to predict 532- and 1064-nm MLA-type, picosecond-domain laser-induced tissue reactions in human skin.

The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment.

Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.

A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis.

LL-37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis (SSc). To elucidate the potential role of LL-37 in SSc. The expression of target molecules was evaluated by immunostaining and quantitative reverse-transcription real-time polymerase chain reaction in human and murine skin. The mechanisms regulating LL-37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation. Serum LL-37 levels were determined by enzyme-linked immunosorbent assay. In SSc lesional skin, LL-37 expression was increased in dermal fibroblasts, perivascular inflammatory cells, keratinocytes and, particularly, dermal small vessels. Expression positively correlated with interferon-α expression, possibly reflecting LL-37-dependent induction of interferon-α. In SSc animal models, bleomycin-treated skin exhibited the expression pattern of CRAMP, a murine homologue of LL-37, similar to that of LL-37 in SSc lesional skin. Furthermore, Fli1+/- mice showed upregulated expression of CRAMP in dermal small vessels. Fli1 binding to the CAMP (LL-37 gene) promoter and Fli1 deficiency-dependent induction of LL-37 were also confirmed in human dermal microvascular endothelial cells. In the analysis of sera, patients with SSc had serum LL-37 levels significantly higher than in healthy controls. Furthermore, serum LL-37 levels positively correlated with skin score and the activity of alveolitis and were significantly elevated in patients with digital ulcers compared with those without. LL-37 upregulation, induced by Fli1 deficiency at least in endothelial cells, potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in SSc.

Human epidermal stem cells: Role in adverse skin reactions and carcinogenesis from radiation

In human skin, keratinopoiesis is based on a functional hierarchy among keratinocytes, with rare slow-cycling stem cells responsible for the long-term maintenance of the tissue through their self-renewal potential, and more differentiated daughter progenitor cells actively cycling to permit epidermal renewal and turn-over every month. Skin is a radio-responsive tissue, developing all types of radiation damage and pathologies, including early tissue reactions such as dysplasia and denudation in epidermis, and later fibrosis in the dermis and acanthosis in epidermis, with the TGF-beta 1 pathway as a known master switch. Also there is a risk of basal cell carcinoma, which arises from epidermal keratinocytes, notably after oncogenic events in PTCH1 or TP53 genes. This review will cover the mechanisms of adverse human skin reactions and carcinogenesis after various types of exposures to ionizing radiation, with comparison with animal data when necessary, and will discuss the possible role of stem cells and their progeny in the development of these disorders. The main endpoints presented are basal cell intrinsic radiosensitivity, genomic stability, individual factors of risk, dose specific responses, major molecular pathways involved and the cellular origin of skin reactions and cancer. Although major advances have been obtained in recent years, the precise implications of epidermal stem cells and their progeny in these processes are not yet fully characterized.

Human skin reactions towards bites of tropical bed bug, Cimex hemipterus F. (Hemiptera: Cimicidae): A preliminary case study

ObjectiveTo observe the manifestation of skin reactions and determine the time for skin reactions from bites of tropical bed bug (Cimex hemipterus) to disappear on different body parts. MethodsForearm, upper arm and shoulder were exposed to tropical bed bugs and the manifestations of skin reactions afterwards were observed up to 144 h. ResultsItches, wheals and lesions were recorded for the three body parts. Itches were felt for about 15 min for all body parts. The wheals were recorded up to an hour before it flattened, and lesions manifested right after that and lasted for several days. One individual of bed bug took the least time for the skin reaction to disappear while shoulder recorded the longest time for the skin reactions to disappear completely. ConclusionsDifferent body parts may produce different skin reactions and the time required for the skin reactions to disappear completely was also varied.

Unique microRNAs appear at different times during the course of a delayed-type hypersensitivity reaction in human skin.

Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression and have been implicated in various inflammatory skin diseases, but their role in DTH reactions is not well understood. We generated global miRNA expression profiles (using next-generation sequencing) of DPCP reactions in skin of seven healthy volunteers at 3, 14 and 120 days after challenge. Compared to placebo-treated sites, DPCP-challenged skin at 3 days (peak inflammation) had 127 miRNAs significantly deregulated. At 14 days (during resolution of inflammation), 43 miRNAs were deregulated and, at 120 days (when inflammation had completely resolved), six miRNAs were upregulated. While some miRNAs have been observed in psoriasis or atopic dermatitis, most of the deregulated miRNAs have not yet been studied in the context of skin biology or immunology. Across the three time points studied, many but not all miRNAs were uniquely expressed. As various miRNAs may influence T cell activation, this may indicate that the miRNAs exclusively expressed at different time points function to promote or resolve skin inflammation, and therefore, may inform on the paradoxical ability of DPCP to treat both autoimmune conditions (alopecia areata) and conditions of ineffective immunity (melanoma).

Estimation of the contribution of human skin and ozone reaction to volatile organic compounds (VOC) concentration in aircraft cabins

The products derived from ozonolysis of organic compounds on the human skin may be an important source of volatile organic compounds (VOC) in aircraft cabins. This study aims to estimate the contribution of human skin and ozone reaction to VOC concentrations in aircraft cabins. Based on the measurements of ozone and VOC concentrations in five flights in March 2013, we estimated the contribution of human skin and ozone reaction to VOC concentration using the first-order kinetic formula. The results show that the prominent volatile products derived from ozonolysis contribution differed from each other, largely due to the difference of the O3 concentrations among different flights. The results of sensitivity analysis show that the disturbance from substrate had evident effect on contribution from products of the squalene and ozone reaction, and the disturbance from substrate had little effect on the contribution from products of the linoleic acid and ozone reaction.

Psoriasis is characterized by deficient negative immune regulation compared to transient delayed-type hypersensitivity reactions

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.

Psoriasis is characterized by deficient negative immune regulation compared to transient delayed-type hypersensitivity reactions.

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.