Unique microRNAs appear at different times during the course of a delayed-type hypersensitivity reaction in human skin.
Unique microRNAs appear at different times during the course of a delayed-type hypersensitivity reaction in human skin.
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DOI：
10.1111/exd.12813
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发表时间：
2015-12
影响因子：
3.6
通讯作者：
Krueger JG
中科院分区：
文献类型：
--
作者：
Gulati N;Løvendorf MB;Zibert JR;Akat KM;Renwick N;Tuschl T;Krueger JG
Diphencyprone (DPCP) 是一种诱导迟发型超敏反应 (DTH) 反应的半抗原。 MicroRNA (miRNA) 是一种短非编码 RNA，可负向调节基因表达，与多种炎症性皮肤病有关，但它们在 DTH 反应中的作用尚不清楚。我们在攻击后 3、14 和 120 天生成了 7 名健康志愿者皮肤中 DPCP 反应的全局 miRNA 表达谱（使用新一代测序）。与安慰剂治疗部位相比，DPCP 激发的皮肤在第 3 天（炎症高峰期）有 127 个 miRNA 显着失调。第 14 天（炎症消退期间），43 个 miRNA 失调，第 120 天（炎症完全消退期间），6 个 miRNA 上调。虽然在牛皮癣或特应性皮炎中观察到了一些 miRNA，但大多数失调的 miRNA 尚未在皮肤生物学或免疫学背景下进行研究。在研究的三个时间点中，许多但并非所有 miRNA 都有独特的表达。由于各种 miRNA 可能影响 T 细胞激活，这可能表明在不同时间点专门表达的 miRNA 具有促进或解决皮肤炎症的功能，因此可能揭示 DPCP 治疗自身免疫性疾病（斑秃）和无效免疫性疾病（黑色素瘤）的矛盾能力。
Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression, and have been implicated in various inflammatory skin diseases, but their role in DTH reactions is not well understood. We generated global miRNA expression profiles (using next-generation sequencing) of DPCP reactions in skin of 7 healthy volunteers at 3, 14, and 120 days after challenge. Compared to placebo-treated sites, DPCP-challenged skin at 3 days (peak inflammation) had 127 miRNAs significantly deregulated. At 14 days (during resolution of inflammation), 43 miRNAs were deregulated and, at 120 days (when inflammation had completely resolved), 6 miRNAs were upregulated. While some miRNAs have been observed in psoriasis or atopic dermatitis, most of the deregulated miRNAs have not yet been studied in the context of skin biology or immunology. Across the three time points studied, many but not all miRNAs were uniquely expressed. As various miRNAs may influence T cell activation, this may indicate that the miRNAs exclusively expressed at different time points function to promote or resolve skin inflammation, and therefore may inform on the paradoxical ability of DPCP to treat both autoimmune conditions (alopecia areata) and conditions of ineffective immunity (melanoma).