Allergic Contact Dermatitis
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.
Available from: Erwin L Roggen
- "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. "
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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 · 3.71 Impact Factor
Available from: Gerald Brandacher
- "Parallels between acute skin rejection and inflammatory dermatoses (e.g., contact dermatitis, psoriasis, and atopic dermatitis) also exist on the molecular and cellular levels. Allergic contact dermatitis, for example, is a T-cell-mediated-delayed-type hypersensitivity reaction that occurs upon hapten challenge in sensitized individuals . Therefore, the differentiation mainly based on histological and macroscopic criteria can be difficult. "
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ABSTRACT: The emerging field of vascular composite allotransplantation (VCA) has become a clinical reality. Building upon cutting edge understandings of transplant surgery and immunology, complex grafts such as hands and faces can now be transplanted with success. Many of the challenges that have historically been limiting factors in transplantation, such as rejection and the morbidity of immunosuppression, remain challenges in VCA. Because of the accessibility of most VCA grafts, and the highly immunogenic nature of the skin in particular, VCA has become the focal point for cross-disciplinary approaches to developing novel approaches for some of the most challenging immunological problems in transplantation, particularly the early diagnoses and assessment of rejection. This paper provides a historically oriented introduction to the field of organ transplantation and the evolution of VCA.
Clinical and Developmental Immunology 02/2013; 2013(2):402980. DOI:10.1155/2013/402980 · 2.93 Impact Factor
Available from: ocean.kisti.re.kr
- "Irritant contact dermatitis accounts for 80% of all contact dermatitis reactions. It occurs as a result of xenobiotic chemicals penetrating the skin and chemically reacting with self proteins, which results in a hapten-specific immune response (17). Exposure to PA causes irritation and can lead to allergic skin disorders such as atopic or contact dermatitis accompanied by irritant dermatitis in the site at which contact with an allergen has occurred (3). "
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ABSTRACT: The purpose of this study was to investigate the anti-allergy activities of persimmon leaf extract (PLE) on a phthalic anhydride (PA)-induced allergic mouse model. A human leukemic mast cell line (HMC-1) was used to examine the inhibitory activity of PLE on the histamine release by human leukemic mast cells. PLE inhibited histamine release from HMC-1 cells in response to cross-linkage of high-affinity IgE receptor-α (FcεRIα). Additionally, a PA-induced allergic mouse model was used to investigate the effects of PLE in vivo. Mice were orally administrated with or without PLE of single dose (250 mg/kg/day) for 31 days. Oral intake of PLE significantly inhibited passive cutaneous reactions. Oral administration of PLE to PA-induced allergic mice also led to a striking suppression of the development of contact dermatitis, ear swelling and lymph node weight. In addition, PA-specific IL-4 production of draining lymph node cells was markedly diminished by PLE oral administration, but not IFN-γ. Furthermore, PLE treatment suppressed PA-induced thymus and activation-regulated chemokine (CCL17) and cutaneous T cell-attracting chemokine (CCL27) expressions in ear tissues. Based on these results, we suggest that PLE may have therapeutic potential as an effective material for management of irritant contact dermatitis or related inflammatory diseases.
Preventive Nutrition and Food Science 03/2012; 17(1):14-21. DOI:10.3746/pnf.2012.17.1.014
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