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

过敏性接触性皮炎（ACD）和刺激性皮炎（ICD）是由外源性化学物质引起的炎症性湿疹性皮肤病。它们属于最重要的职业性皮肤病。病理机制的一个重要组成部分是所谓的危险信号激活先天免疫系统。这些可以是模式识别受体如Toll样受体（TLR）或细胞蛋白质、核酸、ATP和细胞外基质组分的配体。先天免疫系统的激活导致皮肤炎症，并因此导致ACD，导致接触性过敏原特异性T细胞的引发。由于危险信号不必完全或部分地由引起ACD的化学品引起，因此也引起危险信号的其他化学品可以引起缺失的危险信号的替代或微弱的危险信号的增强。这可能会导致意外的过敏和ACD相当弱的接触过敏原。化妆品等消费品以及许多工作材料通常含有许多不同的化学物质，这些化学物质的组合可能导致这种增强效应。在本项目中，我们将通过使用定义的化学组合来分析这种增强效应及其对ACD致敏和激发阶段的影响。该项目的目标是阐明增强效应的机械基础，建立体外测试系统，通过识别危害和风险评估改进预防工作，以保护消费者和从事危险职业的工人。

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.