Up-regulation of Interferon-inducible protein 16 contributes to psoriasis by modulating chemokine production in keratinocytes.
Up-regulation of Interferon-inducible protein 16 contributes to psoriasis by modulating chemokine production in keratinocytes.
复制标题
干扰素诱导蛋白 16 的上调通过调节角质形成细胞中趋化因子的产生而导致牛皮癣
DOI：
10.1038/srep25381
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发表时间：
2016-05-03
影响因子：
4.6
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Cao T;Shao S;Li B;Jin L;Lei J;Qiao H;Wang G
银屑病是一种常见的慢性炎症性皮肤病，以表皮增生和真皮炎症为特征。角质形成细胞活化在银屑病中起着重要作用，但其潜在机制尚不清楚。干扰素诱导蛋白16（IFI 16），先天免疫系统传感器，据报道，影响角质形成细胞的功能。因此，我们假设IFI 16通过调节角质形成细胞活化来促进银屑病。在本研究中，我们证实了IFI 16在银屑病患者的表皮角质形成细胞中过表达。此外，银屑病相关的细胞因子，包括IFN-γ、TNF-α、IL-17和IL-22，通过激活STAT 3信号传导诱导角质形成细胞中IFI 16上调。我们还观察到IFI 16激活TBK 1-NF-κB信号，导致CXCL 10和CCL 20的产生。重要的是，敲低p204（据报道为人IFI 16的小鼠直链）抑制患有咪喹莫特诱导的银屑病样皮炎的小鼠的表皮增生。这些结果表明，IFI 16在银屑病的发病机制中起着关键作用，并可能是一个潜在的治疗靶点。
Psoriasis is a common chronic inflammatory skin disease characterized by epidermal hyperplasia and dermal inflammation. Keratinocyte activation is known to play a critical role in psoriasis, but the underlying mechanism remains unclear. Interferon-inducible protein 16 (IFI16), an innate immune system sensor, is reported to affect keratinocyte function. We therefore hypothesized that IFI16 promotes psoriasis by modulating keratinocyte activation. In the present study, we cinfirmed that IFI16 was overexpressed in epidermal keratinocytes of psoriasis patients. In addition, psoriasis-related cytokines, including IFN-γ, TNF-α, IL-17 and IL-22, induced IFI16 up-regulation in keratinocytes via activation of STAT3 signaling. We also observed that IFI16 activated the TBK1-NF-κB signaling, leading to the production of CXCL10 and CCL20. Importantly, knocking down p204, which is reported as the mouse orthologous of human IFI16, inhibited epidermal hyperplasia in mice with imiquimod-induced psoriasiform dermatitis. These findings indicate that IFI16 plays a critical role in the pathogenesis of psoriasis and may be a potential therapeutic target.