RNase 7 is one of the major antimicrobial peptides (AMPs) secreted by keratinocytes. The AMPs human beta defensin 2 and LL-37 promote the toll-like receptor 9–mediated activation of human plasmacytoid dendritic cells (pDCs) by human self-DNA; however, whether keratinocytes respond in a similar way has not yet been addressed. Keratinocytes express several receptors for the detection of cytosolic DNA. Here, we investigated the activation of keratinocytes by RNase 7 in combination with human DNA. The stimulation of keratinocytes with RNase 7 and human DNA induced a strong increase in the production of IP-10. Of note, the stimulation of keratinocytes with human beta defensin 2 and LL-37 in combination with DNA failed to induce the production of IP-10. The production of IP-10 was mediated by the induction of the type I interferon IFN-β and was significantly downregulated by blocking of the interferon-α/β receptor and inhibition of stimulator of IFN genes. In addition, the pretreatment of keratinocytes with RNase 7 and DNA significantly reduced the herpes simplex virus-1 infection of human keratinocytes. This study demonstrates that RNase 7 functions as an alarmin by converting self-DNA into a danger signal that directly activates an antiviral immune response in human keratinocytes without the involvement of plasmacytoid dendritic cells.

RNase 7是角质形成细胞分泌的主要抗菌肽（AMP）之一。AMPs人β防御素2和LL-37促进人自身DNA通过toll样受体9介导的人浆细胞样树突状细胞（pDC）激活。然而，尚未探讨角质形成细胞是否以类似方式应答。角质形成细胞表达几种用于检测胞质DNA的受体。在这里，我们研究了与人DNA结合的RNase 7对角质形成细胞的激活作用。用RNase 7和人类DNA刺激角质形成细胞可诱导IP-10的产生大量增加。值得注意的是，用人β防御素2和LL-37结合DNA刺激角质形成细胞无法诱导IP-10的产生。IP-10的产生是由I型干扰素IFN-β的诱导介导的，并且由于干扰素-α/β受体的阻滞和对IFN基因刺激的抑制而显着下调。此外，用RNase 7和DNA预处理角质形成细胞可显着减少人角质形成细胞的单纯疱疹病毒1感染。这项研究表明，RNase 7通过将自身DNA转化为危险信号而起警报蛋白的作用，该信号直接激活人角质形成细胞中的抗病毒免疫反应，而浆细胞样树突状细胞不参与其中。