Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Dermatol Sci. 2023 Aug;111(2):43-51. doi: 10.1016/j.jdermsci.2023.07.004. Epub 2023 Jul 20.
IFN-ε is essential in combating viral infections, particularly in epithelial cells and protected mucosal tissues. Its protective effects have been demonstrated against HSV2, Zika virus, HIV and SARS-COV2. However, the specific expression and role of IFN-ε in skin keratinocytes and HPV infection are still not fully understood and require further investigation.
In this study, we aimed to investigate the functions and expression mechanism of IFN-ε in keratinocytes during HPV infection and the progression of condyloma acuminata.
Keratinocytes isolated from biopsied CA warts and normal skins samples were analyzed by MeRIP-seq analysis. IFN-ε and WTAP in CA warts and normal skins were analyzed by immunostaining and qPCR.
In this study, we identified IFN-ɛ was markedly upregulated in CA warts and HPV-infected keratinocytes. IFN-ɛ expression also showed negatively correlation with the size of CA warts (R=-0.4646, P = 0.009). IFN-ɛ suppressed the susceptibility of HPV infection directly. m6A analysis reveals WTAP is a key m6A writer promoting the m6A modification of IFNE mRNA.
Our research suggests that IFN-ɛ is an important Type I IFN cytokine involved in the development of genital warts. Furthermore, we found that HPV infection affects the m6A modifications of IFNE through a mechanism dependent on WTAP. This study provides insights into the innate immune response of the host to HPV infection and may contribute to the development of future strategies for regulating innate immunity to treat genital warts.
IFN-ε 在对抗病毒感染方面至关重要，特别是在上皮细胞和受保护的黏膜组织中。它已被证明对单纯疱疹病毒 2 型、寨卡病毒、HIV 和 SARS-COV2 具有保护作用。然而，IFN-ε 在皮肤角质形成细胞和 HPV 感染中的具体表达和作用仍不完全清楚，需要进一步研究。
本研究旨在探讨 IFN-ε 在 HPV 感染和尖锐湿疣进展过程中角质形成细胞中的功能和表达机制。
通过 MeRIP-seq 分析对活检的 CA 疣和正常皮肤样本中的角质形成细胞进行分析。通过免疫染色和 qPCR 分析 CA 疣和正常皮肤中的 IFN-ε 和 WTAP。
本研究中，我们发现 IFN-ɛ 在 CA 疣和 HPV 感染的角质形成细胞中明显上调。IFN-ɛ 的表达与 CA 疣的大小呈负相关（R=-0.4646，P=0.009）。IFN-ɛ 直接抑制 HPV 感染的易感性。m6A 分析表明 WTAP 是一种关键的 m6A 书写蛋白，可促进 IFNE mRNA 的 m6A 修饰。
我们的研究表明 IFN-ɛ 是一种参与生殖器疣发生的重要 I 型 IFN 细胞因子。此外，我们发现 HPV 感染通过依赖 WTAP 的机制影响 IFNE 的 m6A 修饰。这项研究为宿主对 HPV 感染的固有免疫反应提供了新的见解，并可能有助于开发调节固有免疫治疗生殖器疣的未来策略。
