PDF(Pubmed)
Abstract：
Atopic dermatitis (AD) is symptomatically worse in the evening, but the mechanism driving nocturnal eczema remains elusive. Our objective was to determine the circadian rhythm of skin barrier function measured by transepidermal water loss (TEWL) in AD patients and explore the molecular underpinnings. A pilot study was performed on a diverse group of AD (n = 4) and control (n = 2) young patients. We used an inpatient tightly controlled, modified, constant routine protocol. TEWL was measured at least every 90 min in the antecubital fossa (lesional) and forearm, while whole blood samples were collected every 4 h. Results show a significant difference in the antecubital fossa TEWL in the AD group versus controls. TEWL in control skin decreases starting a few hours prior to bedtime, both in the antecubital fossa and in the forearm, while in the AD forearm skin, pre-bedtime TEWL increases. We identified 1576 differentially expressed genes using a time-dependent model. The top 20 upregulated gene ontology pathways included neuronal pathways, while the downregulated functional terms included innate immune signaling and viral response. Similar pathways positively correlated with forearm TEWL in controls and inversely with the AD group. Upregulation in sensory perception pathways correlated with increases in lesional (antecubital fossa) TEWL in the evening. Results show skin barrier function worsens in the evening in the AD group, at a time when barrier is normally rejuvenating in healthy skin. This timing and the detection of transcriptomic signatures of sensory perception and diminished viral response might correspond to the nocturnal itch. Larger studies are needed to evaluate these associations in the skin.
摘要：
特应性皮炎（AD）在晚上症状加重，但是驱动夜间湿疹的机制仍然难以捉摸。我们的目的是确定AD患者通过经皮失水（TEWL）测量的皮肤屏障功能的昼夜节律，并探索分子基础。对不同组的AD（n=4）和对照（n=2）年轻患者进行了初步研究。我们使用了一个严格控制的住院病人，已修改,恒定的常规协议。在肘前窝（病变）和前臂至少每90分钟测量一次TEWL，而每4小时收集全血样本。结果表明，AD组与对照组相比，肘前窝TEWL存在显着差异。从睡前几小时开始，对照皮肤的TEWL下降，在肘前窝和前臂，而在AD前臂皮肤中，睡前TEWL增加。我们使用时间依赖性模型鉴定了1576个差异表达的基因。前20个上调的基因本体论通路包括神经元通路，而下调的功能术语包括先天免疫信号和病毒应答。在对照组中，类似的途径与前臂TEWL呈正相关，而与AD组呈负相关。感觉知觉途径的上调与晚上病灶（肘前窝）TEWL的增加有关。结果显示AD组皮肤屏障功能在晚上恶化,在屏障通常在健康皮肤中恢复活力的时候。这种时机和感觉感知的转录组特征的检测和减弱的病毒反应可能对应于夜间瘙痒。需要更大的研究来评估皮肤中的这些关联。
