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

刺激性（ICD）和过敏性接触性皮炎（ACD）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先天免疫系统被所谓的危险信号激活。这些可以是模式识别受体的配体，如toll样受体（TLR），或细胞蛋白，核酸，ATP和细胞外基质成分。先天免疫系统的激活导致皮肤炎症，因此，在ACD中，接触过敏原特异性T细胞的启动。由于危险信号不必完全或部分由引起acd的化学物质引起，其他同样引起危险信号的化学物质也可以引起缺失危险信号的补充或微弱危险信号的增强。这可能导致意想不到的致敏和ACD由相当弱的接触过敏原。消费品，如化妆品，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。在这个项目中，我们将通过使用确定的化学组合来分析这种增强效应及其对ACD敏化和引发阶段的影响。本项目的目的是阐明增强效应的机理基础，建立体外试验体系，通过识别危害和风险评估来改进预防措施，以保护消费者和高危职业的工人。

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.