Patients with co-existing psoriasis and eczema: key to understand the pathogenesis of chronic inflammatory skin diseases

慢性炎症性皮肤病，如牛皮癣或湿疹，对现代医学构成挑战，因为它们经常发生，对受影响的患者意味着毁灭性的生活质量，并带来沉重的社会经济负担。这些复杂的疾病是基于个体易感性、调节环境因素和改变的免疫反应。虽然在阐明慢性炎症性皮肤病的发病机制方面取得了许多进展，但一些基本问题仍未得到解答：“这种疾病的主要诱因是什么？”或“是什么导致了这种疾病的慢性病程？”这些未解之谜的一个原因是牛皮癣和湿疹的异质性。为了取得实质性的进展，需要一种能够区分病变皮肤中个体遗传密码和分子表达变化的模型。这样一个模型是本应用的基础：同时存在牛皮癣和湿疹的患者。这种跨学科的方法将比较同时受牛皮癣和湿疹影响的患者皮损中的分子事件。在这些患者中，可以观察到相同遗传背景下不同疾病的表达变化。这是很重要的，因为到目前为止，只有表达变化可以治疗性地调节。在一种炎症性皮肤状况中特异性调节的因子代表了非常有希望的诊断和治疗靶点。在初步研究中，我们发现NOS2和CCL27分别是银屑病和湿疹中特异性和高度调控的标志物。在这里，我们将验证这两个标记并对其进行功能表征。此外，系统的计算生物学方法将确定进一步的候选靶点。

Chronic inflammatory skin diseases such as psoriasis or eczema challenge modern medicine, as they are frequent, mean a devastating life quality for affected patients and come with a high socio-economic burden. Those complex diseases are based on individual predisposition, modulating environmental factors, and altered immune responses. While a lot of progress was made elucidating the pathogenesis of chronic inflammatory skin diseases, basic questions remain unanswered: "what are primary triggers of the disease?" or "What leads to chronic course of the disease?". A reason for those unresolved riddles is the heterogeneity of both psoriasis and eczema. To achieve a substantial progress, a model is needed that enables to distinguish the individual genetic code from molecular expression changes in lesional skin. Such a model is the basis of this application: patients with co-existing psoriasis and eczema.This interdisciplinary approach will compare molecular events in lesional skin in patients affected by both psoriasis and eczema at the same time. In these patients, it is possible to observe expression changes of different diseases at the same genetic background. This is important, as so far only expression changes can be modulated therapeutically. Factors that are regulated specifically in one inflammatory skin condition represent highly promising diagnostic and therapeutic targets. In pilot studies, we identified NOS2 and CCL27 as specifically and highly regulated markers in psoriasis or eczema, respectively. Here, we will validate and functionally characterize those two markers. Furthermore, systematic computational biology approaches will identify further candidate targets.