RNA helicases play roles in various essential biological processes such as RNA splicing and editing. Recent in vitro studies show that RNA helicases are involved in immune responses toward viruses, serving as viral RNA sensors or immune signaling adaptors. However, there is still a lack of in vivo data to support the tissue- or cell-specific function of RNA helicases owing to the lethality of mice with complete knockout of RNA helicases; further, there is a lack of evidence about the antibacterial role of helicases. Here, we investigated the in vivo role of Dhx15 in intestinal antibacterial responses by generating mice that were intestinal epithelial cell (IEC)-specific deficient for Dhx15 (Dhx15 f/f Villin1-cre, Dhx15^ΔIEC). These mice are susceptible to infection with enteric bacteria Citrobacter rodentium (C. rod), owing to impaired α-defensin production by Paneth cells. Moreover, mice with Paneth cell-specific depletion of Dhx15 (Dhx15 f/f Defensinα6-cre, Dhx15^ΔPaneth) are more susceptible to DSS (dextran sodium sulfate)-induced colitis, which phenocopy Dhx15^ΔIEC mice, due to the dysbiosis of the intestinal microbiota. In humans, reduced protein levels of Dhx15 are found in ulcerative colitis (UC) patients. Taken together, our findings identify a key regulator of Wnt-induced α-defensins in Paneth cells and offer insights into its role in the antimicrobial response as well as intestinal inflammation.

RNA 解旋酶在各种重要的生物学过程中发挥作用，例如 RNA 剪接和编辑。最近的体外研究表明，RNA 解旋酶参与针对病毒的免疫反应，充当病毒 RNA 传感器或免疫信号转导接头。然而，由于完全敲除 RNA 解旋酶的小鼠具有致死性，因此仍然缺乏支持 RNA 解旋酶的组织或细胞特异性功能的体内数据；此外，缺乏关于解旋酶抗菌作用的证据。在这里，我们通过生成肠上皮细胞 (IEC) 特异性 Dhx15 缺陷小鼠（Dhx15 f/f Villin1-cre，Dhx15 ^ΔIEC），研究了 Dhx15 在肠道抗菌反应中的体内作用。这些老鼠很容易感染肠道细菌柠檬酸杆菌( C. rod )，由于潘氏细胞产生的 α-防御素受损。此外，Dhx15 Paneth 细胞特异性缺失的小鼠（Dhx15 f/f Defensinα6-cre，Dhx15 ^ΔPaneth）更容易受到 DSS（葡聚糖硫酸钠）诱导的结肠炎的影响，由于肠道菌群失调，其表型与 Dhx15 ^ΔIEC小鼠相同微生物群。在人类中，溃疡性结肠炎 (UC) 患者的 Dhx15 蛋白水平降低。综上所述，我们的研究结果确定了潘氏细胞中 Wnt 诱导的 α-防御素的关键调节因子，并提供了对其在抗菌反应和肠道炎症中的作用的深入了解。