Avoiding contact allergens: from basic research to the in vitro identification of contact allergens.

Allergic contact dermatitis (ACD) is a chemical-induced inflammatory skin disease. Contact allergens are low-molecular-weight chemicals that must react with proteins in order to become immunogenic. This interaction leads to the activation of innate immune and stress responses and to the formation of antigenic epitopes for T cells which are the effector cells of ACD. Due to the multitude of chemicals that surround us in our daily life and their potential sensitizing capacity, it is crucial to identify contact sensitizers before these chemicals are used in consumer products. Appropriate in vitro assays for hazard identification are urgently needed to replace animal-based assays. The EU-wide ban on sensitization testing of cosmetic ingredients in animals is in effect since March 2009 and the necessity to test more than 30,000 already marketed chemicals for their sensitizing potential under the EU regulation REACh has intensified the worldwide efforts to replace animal testing. We summarize here the current strategies to develop a battery of assays which allows the identification of contact allergens by in vitro alternatives to animal testing. Our main focus lies on the test systems recently developed within the EU project Sens-it-iv in which we participate.

Mechanisms of chemical-induced innate immunity in allergic contact dermatitis.

Allergic contact dermatitis (ACD) is one of the most prevalent occupational skin diseases and causes severe and long-lasting health problems in the case of chronification. It is initiated by an innate inflammatory immune response to skin contact with low molecular weight chemicals that results in the priming of chemical-specific, skin-homing CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 cells. Following this sensitization step, T lymphocytes infiltrate the inflamed skin upon challenge with the same chemical. The T cells then exert cytotoxic function and secrete inflammatory mediators to produce an eczematous skin reaction. The recent characterization of the mechanisms underlying the innate inflammatory response has revealed that contact allergens activate innate effector mechanisms and signalling pathways that are also involved in anti-infectious immunity. This emerging analogy implies infection as a potential trigger or amplifier of the sensitization to contact allergens. Moreover, new mechanistic insights into the induction of ACD identify potential targets for preventive and therapeutic intervention. We summarize here the latest findings in this area of research.

Innate and adaptive immune responses in contact dermatitis: analogy with infections.

Allergic contact dermatitis (ACD) is an inflammatory skin disease of great and steadily increasing importance as an occupational health problem. The disease is induced by chemicals and metal ions which penetrate the skin and form complexes with host proteins. This process is accompanied by a strong, allergen-induced inflammatory reaction and leads to the migration of allergen-carrying dendritic cells (DC) from the skin to regional lymph nodes, where they promote generation of allergen-specific T cells. The latter are the ultimate effector cells of the disease. Re-exposure to the causative agent leads to the recruitment of the T effector cells, which then elicit the typical skin inflammatory reaction at the site of contact. Although DC and effector T cells play a protagonistic role in the sensitization and elicitation phase of ACD, respectively, other cell types including keratinocytes, NK cells, mast cells and B cells contribute to the pathogenesis of the disease. In this review the authors summarize recent findings that identify stress responses and innate immune pathways triggered by contact allergens and review recent data regarding the adaptive T cell response. The new data were collected mainly from studies on contact hypersensitivity (CHS), the corresponding experimental mouse model of human ACD. The elucidation of the molecular events involved in contact allergen-induced innate responses will help to design new treatment strategies and may allow to develop predictive in vitro assays for the identification of contact allergens.