Inflammasomes are immune complexes whose activation leads to the release of pro-inflammatory cytokines IL-18 and IL-1β. Type I IFNs play a role in fighting infection and stimulate the expression of IFN-stimulated genes (ISGs) involved in inflammation. Despite the importance of these cytokines in inflammation, the regulation of inflammasomes by type I IFNs remains poorly understood. Here, we analysed RNA-sequencing data from patients with monogenic interferonopathies and found an up-regulation of several inflammasome-related genes. To investigate the effect of type I IFN on the inflammasome, we treated human monocyte-derived macrophages with IFN-α and observed an increase in CASP1 and GSDMD mRNA levels over time, whereas IL1B and NLRP3 were not directly correlated to IFN-α exposure time. IFN-α treatment reduced the release of mature IL-1β and IL-18, but not caspase-1, in response to ATP-mediated NLRP3 inflammasome activation, suggesting regulation occurs at cytokine expression levels and not the inflammasome itself. However, more studies are required to investigate how regulation by IFN-α occurs and impacts NLRP3 and other inflammasomes at both transcriptional and post-translational levels.

中文翻译：

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I 型干扰素调节人巨噬细胞中白细胞介素 1β 和 IL-18 的产生和分泌。

炎症小体是免疫复合物，其激活导致促炎细胞因子 IL-18 和 IL-1β 的释放。 I 型干扰素在对抗感染和刺激参与炎症的干扰素刺激基因 (ISG) 的表达中发挥作用。尽管这些细胞因子在炎症中很重要，但 I 型干扰素对炎症小体的调节仍知之甚少。在这里，我们分析了单基因干扰素病患者的 RNA 测序数据，发现一些炎症小体相关基因的上调。为了研究 I 型 IFN 对炎症小体的影响，我们用 IFN-α 处理人单核细胞来源的巨噬细胞，观察到CASP1和GSDMD mRNA 水平随时间的推移而增加，而IL1B和NLRP3与 IFN-α 暴露时间没有直接相关。 IFN-α 治疗减少了成熟 IL-1β 和 IL-18 的释放，但不减少 caspase-1，以响应 ATP 介导的 NLRP3 炎症小体激活，表明调节发生在细胞因子表达水平，而不是炎症小体本身。然而，还需要更多的研究来调查 IFN-α 的调节如何发生以及如何在转录和翻译后水平影响 NLRP3 和其他炎症小体。