ADAM17-Deficient Mice Model the Transcriptional Signature of Human Atopic Dermatitis.
ADAM17-Deficient Mice Model the Transcriptional Signature of Human Atopic Dermatitis.
复制标题
ADAM17 缺陷小鼠模拟人类特应性皮炎的转录特征。
DOI：
10.1016/j.jid.2018.04.021
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Nagao,Keisuke
中科院分区：
文献类型：
--
作者：
Woodring,Therese;Kobayashi,Tetsuro;Kim,Doyoung;Nagao,Keisuke
特应性皮炎（AD）是一种以屏障缺陷、免疫失调和微生物生态失调为特征的炎症性皮肤病。AD经常先于其他屏障组织的特应性疾病，如食物过敏和哮喘（damage etáal）。, 2014)。尽管这种疾病的流行和影响，仍然有很少的类固醇节约治疗选择，只有一种靶向治疗被美国食品和药物管理局批准（Simpson etáal）。， 2016)，反映了当前知识和干预策略的局限性。为了进一步了解其发病机制和治疗方法，需要一个健全的临床前动物模型。在包括表皮在内的表达sox9的组织中缺乏Adam17的小鼠（Adam17 fl/fl Sox9-Cre，以下简称A17）先前已被确定为基于湿疹表型和A17皮肤自发性葡萄球菌生态失调的严重人类AD的模型（Kobayashi etáal）。, 2015)。虽然有用，但这些终点只捕获了AD最严重的异常特征，并不能验证尚不清楚的发病机制模型。为了解决这些局限性，我们分析了A17小鼠皮肤中整个皮肤转录组的无偏变化。所有实验都是在国家癌症研究所动物护理和使用委员会批准的动物研究计划下进行的。
Atopic dermatitis (AD) is an inflammatory skin disease characterized by barrier defect, immune dysregulation, and microbial dysbiosis. AD frequently precedes atopic disease at other barrier tissues, such as food allergies and asthma (Dharmage etáal., 2014). Despite the prevalence and impact of the disease, there are still few steroid-sparing treatment options and only one targeted therapy approved by the US Food and Drug Administration (Simpson etáal., 2016), reflecting the limits of current knowledge and strategies for intervention.To advance understanding of pathogenesis and treatment, a robust preclinical animal model is needed. Mice lacking Adam17 in Sox9-expressing tissue including epidermis (Adam17 fl/fl Sox9-Cre, henceforth A17) have been previously identified as a model for severe human AD based on the eczematous phenotype and spontaneous staphylococcal dysbiosis of A17 skin (Kobayashi etáal., 2015). Although useful, these endpoints capture only the most grossly aberrant features of AD and cannot validate the model for as-yet-unknown mechanisms of pathogenesis. To address these limitations, we analyzed unbiased changes across the entire skin transcriptome in A17 mouse skin. All experiments were performed under an animal study proposal approved by the National Cancer Institute Animal Care and Use Committee.