Divergent E1 and E2 epithelial differentiation and associated regulatory mechanisms of IL-20 family members

过敏症影响20%的人口，并有增加的趋势。致敏的原因，特别是致敏的机制尚不清楚。上皮细胞在这一过程中发挥着重要作用，因为它们不仅形成了屏障，而且在抗原进入生物体时有助于第一次上下文识别。到目前为止，还不知道上皮细胞经历了分化，使细胞极化为亲过敏的E2型或可能对感染重要的E2型。T细胞或巨噬细胞也观察到这种表型印迹。初步证据表明，这种分化也调节了上皮细胞的免疫调节机制，特别是IL-20家族的免疫调节机制。这组基因被怀疑参与抗炎反应，并可能与呼吸道炎症后的康复有关。因此，探索上皮分化机制以及多潜能的上皮前体细胞是否受到影响是该研究提案的一个关键目标，因为这些与上皮表面的再生有关。事实上，初步数据表明，E2启动发生在基底细胞水平，并且在家尘螨致敏小鼠的气管基底细胞中，E2启动显着增加。对这一水平的影响可能会对受影响的患者产生持续的影响。此外，该项目希望阐明不同的上皮表型是否会引起对细菌病原体的不同反应，而细菌病原体通常在哮喘等呼吸道疾病的恶化中发挥作用。IL-20家族的调节是研究的重点，因为介质被认为是介导上皮恢复的介质。由于呼吸道上皮细胞很容易获得新的治疗方法，本研究为过敏性呼吸道疾病开辟了新的治疗选择。

Allergy affects 20% of the population with an increasing trend. The cause and in particular the mechanism of sensitization are yet unknown. Epithelial cells are playing an important role in this process as they are not only forming a barrier, but also contribute to the first context recognition when the antigen is entering the organism. So far, it was not known that epithelial cells undergo a differentiation that polarizes the cells either to a pro-allergic E2-type or an E2 type that is likely to be important for infections. This kind of phenotype imprinting was observed also for T cells or macrophages. Preliminary evidences suggest that this differentiation also modulates epithelial mechanisms of immune regulation, particularly those of the IL-20 family. This group of genes is suspected in anti-inflammatory responses and could be relevant for reconvalescense following airway inflammation. It is therefore a key objective of the research proposal to explore the epithelial differentiation mechanisms and also whether pluripotent epithelial precursor cells are affected, since these are relevant for the regeneration of the epithelial surface. In fact preliminary data suggest that E2 priming occurs on the basal cell level and that E2 priming is dramatically increased in basal cells of trachea of house dust mite sensitized mice. An impact on this level could have a sustained effect for affected patients. In addition the project wants to elucidate whether the distinct epithelial phenotypes give rise to differential responses to bacterial pathogens that are commonly playing a role in exacerbation of airways diseases such as asthma. The regulation of the IL-20 family is a focus of the study readouts as the mediators are thought to mediate epithelial recovery. Since the airway epithelium is well accessible for novel therapeutics, the proposed research can open novel therapeutic option for allergic airway diseases.