DExD/H盒解旋酶广泛参与核酸识别信号通路的调控，DDX60作为该家族的一员，在系统性红斑狼疮（Systemic lupus erythematosus，SLE）患者细胞中显著上调，但其对于SLE发病的意义并不清楚。

我们通过研究发现，SLE 患者外周血单个核细胞（Peripheral blood mononuclear cells ，PBMCs）中DDX60的表达水平相较于健康对照升高达6倍，且其表达量与I型干扰素特征评分以及疾病活动度呈正相关关系。同时，DDX60的表达受多种促炎细胞因子诱导，IFN-α、IFN-γ和IL-6可通过IFNAR1依赖或非依赖的途径上调DDX60表达。进一步研究发现，DDX60能够促进dsDNA诱导的IFN-I产生，且该生物学效应依赖于cGAS-STING信号通路。机制方面，DDX60对STING及下游信号通路无明显影响，但可与cGAS在dsDNA存在的情况下相互作用，提示DDX60可能通过结合cGAS调控下游信号通路。

综上所述，我们鉴定出一个cGAS-STING信号通路新的正向调控分子DDX60。SLE患者中高水平的DDX60可能参与到疾病发生发展过程。我们的研究为cGAS-STING信号通路的调控提供了新的机制，也为SLE的治疗提供了新的潜在靶点。

DExD/H-box helicases are extensively involved in the regulation of nucleic acid-sensing signaling pathways. As a member of this family, DDX60 is significantly upregulated in cells from systemic lupus erythematosus (SLE) patients, though its role in SLE pathogenesis remains unclear.

Our study revealed that the expression level of DDX60 in peripheral blood mononuclear cells (PBMCs) of SLE patients was approximately 6-fold higher than in healthy controls, showing positive correlations with both type I interferon signature scores and disease activity. Furthermore, DDX60 expression could be induced by various proinflammatory cytokines, with IFN-α, IFN-γ, and IL-6 upregulating its expression through either IFNAR1-dependent or -independent pathways. Further investigation demonstrated that DDX60 enhances dsDNA-induced IFN-I production, an effect dependent on the cGAS-STING signaling pathway. Mechanistically, while DDX60 showed no direct impact on STING or downstream signaling components, it was found to interact with cGAS in the presence of dsDNA, suggesting that DDX60 may regulate downstream signaling through its association with cGAS.

In summary, we have identified DDX60 as a novel positive regulator of the cGAS-STING signaling pathway. The elevated DDX60 levels in SLE patients may contribute to disease progression. Our findings not only provide new insights into the regulatory mechanisms of the cGAS-STING pathway but also suggest a potential therapeutic target for SLE treatment.