Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA.
Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Sci Adv. 2020 Apr 1;6(14):eaay3245. doi: 10.1126/sciadv.aay3245. eCollection 2020 Apr.
In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27-mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus.
在皮肤中，抗病毒蛋白和其他免疫分子是先天抗病毒防御的第一道防线。在这里，我们鉴定并描述了皮肤中先天抗病毒蛋白对 IL-27 的反应及其在抵抗寨卡病毒感染中的功能作用。用 IL-27 处理的表皮角质形成细胞的转录组和表型分析表明，在小鼠和人类的皮肤中，抗病毒蛋白 OAS1、OAS2、OASL 和 MX1 的诱导。发现 IL-27 介导的抗病毒蛋白诱导是在 STAT1 和 IRF3 依赖性但 STAT2 非依赖性的方式下发生的。此外，使用 IL27ra 小鼠，我们证明了 IL-27 在抑制皮肤而非静脉接种后寨卡病毒发病率和死亡率方面的重要作用。总之，我们的结果表明，IL-27 在针对寨卡病毒的皮肤先天抗病毒免疫中具有关键作用，而以前并未被认识到。
