Mechanisms of augmentation of contact allergic reactions by irritants and contact allergens

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Irritant (ICD) and allergic contact dermatitis (ACD) are inflammatory eczematous skin diseases which are induced by xenobiotic chemicals. They belong to the most important occupation-related skin diseases. An essential component of the pathomechanism is the activation of the innate immune system by so-called danger signals. These can be ligands for pattern recognition receptors such as the Toll-like receptors (TLR), or cellular proteins, nucleic acids, ATP and extracellular matrix components. Activation of the innate immune system results in skin inflammation and, consequently, in ACD, in the priming of contact allergen-specific T cells. Since the danger signals do not have to be induced solely or in part by the ACD-causing chemical other chemicals which also elicit danger signals can cause the replacement of missing or the augmentation of weak danger signals. This can result in unexpected sensitizations and ACD by rather weak contact allergens. Consumer products such as cosmetics, but also many working materials normally contain a number of different chemicals the combination of which may be responsible for such augmentation effects.In this project we will analyze such augmentation effects and their impact on the sensitization and elicitation phase of ACD by using defined chemical combinations. The goal of this project is the elucidation of the mechanistic basis of augmentation effects, establishment of an in vitro test system and improvement of the prevention by identification of hazards and risk assessment for the protection of the consumer and workers in occupations at risk.