Allergic Contact Dermatitis
ABSTRACT Allergic contact dermatitis is a classic example of a cell mediated hypersensitivity reaction in the skin. This occurs as a result of xenobiotic chemicals penetrating into the skin, chemically reacting with self proteins, eventually resulting in a hapten-specific immune response. It is precisely because of this localized immune response that allergic signs and symptoms occur (redness, edema, warmth and pruritus). It has been known for years that conventional T-cells (CD4+ or CD8+ T-cells that express a T-cell receptor alpha/Beta) are critical effectors for this reaction. There is emerging evidence that innate immune lymphocytes such as invariant Natural killer T-cells and even Natural killer cells may play important role. Other T-cell types such as Tregulatory cells and the IL-10 secreting Tregulatory cells type I are likely to be important in the control (resolution) of allergic contact dermatitis. Other cell types that may contribute include B-cells and hapten-specific IgM. Additionally, epidermal Langerhans cells have been ascribed an indispensable role as an antigen presenting cell to educate T-cells of the skin immune system. Studies of mice that lack this cell type suggest that Langerhans cells may be dispensible, and may even play a regulatory role in allergic contact dermatitis. The identity of the antigen presenting cells that complement Langerhans cells has yet to be identified. Lastly, Keratinocytes play a role in all phases of allergic contact dermatitis, from the early initiation phase with the elaboration of inflammatory cytokines, that plays a role in Langerhans cell migration, and T-cell trafficking, through the height of the inflammatory phase with direct interactions with epidermotrophic T-cells, through the resolution phase of allergic contact dermatitis with the production of anti-inflammatory cytokines and tolerogenic antigen presentation to effector T-cells. As the understanding of allergic contact dermatitis continues to improve, this will provide novel therapeutic targets for immune modulating therapy.
- SourceAvailable from: Erwin L Roggen
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- "c o m / l o c a t e / y t a a p integration into in vitro assays to both identify contact sensitizers (yes/no answer) and also to determine sensitizer potency. KC play a role in all phases of allergic contact dermatitis, from the early initiation phase with penetration through the stratum corneum (bioavailability), the secretion of inflammatory cytokines required for LC migration and Tcell trafficking, the peak of the inflammatory phase with direct interactions with epidermotrophic T-cells, through to the resolution phase of allergic contact dermatitis with the production of anti-inflammatory cytokines and tolerogenic antigen presentation to effector T-cells (Adler et al., 2011; Gober and Gaspari, 2008). Within the Framework 6 (FP6) European financed project Sens-it-iv 2005–2011, the NCTC2544 IL-18 assay was developed to identify contact sensitizers. "
ABSTRACT: The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC50) with human and animal data showed a superior correlation with human DSA05 (μg/cm(2)) data (spearman r=0.8500; P value (two-tailed)=0.0061) compared to LLNA data (spearman r=0.5968; P value (two-tailed)=0.0542). DSA05=induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA05 data (spearman r=0.8333; P value (two-tailed)=0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model.Toxicology and Applied Pharmacology 07/2013; 272(2). DOI:10.1016/j.taap.2013.07.003
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- "First, the OVA-induced immune response is predominantly a Type I hypersensitivity response involving the production of allergen-specific antibodies, whereas the nickel-and DNFB-induced immune responses are predominantly Type IV hypersensitivity reactions, which is a cell-mediated immune response. For instance, the sensitization and functional end line responses are different in the two responses: sensitization for DNFB involves Langerhans cells presenting antigen to T H 1 cells (Gober and Gaspari 2008), whereas OVA involves airway dendritic cells presenting antigen to T H 2 cells (Lambrecht, Hoogsteden, and Pauwels 2001). Although speculative, one hypothesis is that CB 1 and/or CB 2 is critical for Langerhans cell function but not airway dendritic cells. "
ABSTRACT: The mechanisms by which cannabinoid receptors CB(1) and CB(2) modulate immune function are not fully elucidated. Critical tools for the determination of the role of both receptors in the immune system are CB(1)/CB(2) double null mice (CB(1)/CB(2) null), and previous studies have shown that CB(1)/CB(2) null mice exhibit exaggerated responses to various immunological stimuli. The objective of these studies was to determine the magnitude to which CB(1)/CB(2) null mice responded to the respiratory allergen ovalbumin (OVA) as compared with wild-type C57BL/6 mice. The authors determined that in the absence of adjuvant, both wild-type and CB(1)/CB(2) null mice mounted a marked response to intranasally instilled OVA as assessed by inflammatory cell infiltrate in the bronchoalveolar lavage fluid (BALF), eosinophilia, induction of mucous cell metaplasia, and IgE production. Many of the endpoints measured in response to OVA were similar in wild-type versus CB(1)/CB(2) null mice, with exceptions being modest reductions in OVA-induced IgE and attenuation of BALF neutrophilia in CB(1)/CB(2) null mice as compared with wild-type mice. These results suggest that T-cell responses are not universally exaggerated in CB(1)/CB(2) null mice.Toxicologic Pathology 02/2010; 38(3):382-92. DOI:10.1177/0192623310362706
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ABSTRACT: Allergic contact dermatitis (ACD) is a common skin disorder that has a high socio-economic impact with regard to the increasing number of industrial allergens that has potential harmful effect on the skin of manual workers. Its management relies on the use of topical anti-inflammatory drugs as well as the avoidance of the allergens inducing the disease. However, with regard to the ubiquitous character of many chemicals in the environment, treatment of the disease remains unsatisfactory. Understanding the molecular basis of the disease is of major importance in prospect of designing new therapeutic modalities. In this article, the various stages of the disease are reviewed as well as the recent advances in the understanding of the molecular basis of the mechanisms of the disease that would help to conceive new concepts for drug intervention. The article also reviews some of the recent patent relevant to the field.Recent Patents on Inflammation & Allergy Drug Discovery 02/2008; 2(3):226-31. DOI:10.2174/187221308786241901