In vitro model of altered epidermal barrier indicates roles for as yet unsuspected receptors
Journal of Investigative Dermatology(2018)
摘要
Atopic dermatitis (AD) is a skin disease resulting from interplay between epidermal barrier alterations and abnormal activation of Th2 immune response. An in vitro model of this condition was developed, based on reconstructed human epidermis (RHE) in which membrane cholesterol was first depleted from keratinocytes using methyl-β-cyclodextrin (MβCD) because this treatment had been proved to mimic the AD-altered transcriptomic profile in keratinocytes. After this first challenge, RHE were incubated with cytokines highly expressed in AD lesions: IL-4, -13 and -25. Interestingly, typical AD-features induced by combined challenges (MβCD and ILs) were found more pronounced than when using ILs alone, indicating potential regulation of IL receptors. IL-4 and -13 act mostly via the heterodimeric IL-4Rα/IL-13Rα1 receptor. IL-13 also interacts through IL-13Rα2, known as a decoy receptor overexpressed in AD lesions. Of interest, induction of IL-4Rα, IL-13Rα1 as well as of IL-13Rα2 mRNA expressions is observed by microarray analysis in keratinocytes challenged by MβCD. RT-qPCR analysis confirmed overexpression of IL-13Rα2, in monolayers inside RHE treated with MβCD. Conversely, alterations in IL-4Rα or IL-13Rα1 expression levels were not confirmed in monolayer cultures. IL-4 is able to signal through the IL-4Rα/IL-2Rγ receptor when partners are both expressed. To our surprise, IL-2Rγ was found among the most highly overexpressed genes after microarray analysis of RHE treated with IL-4, -13 and -25. This was confirmed by RT-qPCR analysis. Since IL-2Rγ is normally absent in keratinocytes, this finding opens potentially novel pathways for signaling by ILs in keratinocytes during inflammation and supports potency for new studies in the above described in vitro model.
更多查看译文
关键词
altered epidermal barrier,vitro model
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要