cGAS-STING在过敏性疾病发病机制中的新兴作用
Emerging role of cGAS-STING in the pathogenesis of allergic diseases.
文献信息
| PMID | 42837792 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Hongquan Wang |
| 作者单位 | Inner Mongolia Key Laboratory of Allergic Diseases, Foundational and Translational Medical Research Center, Department of Allergy and General Surgery, Hohhot First Hospital, Hohhot 010030, China. |
| 期刊 | International immunopharmacology |
| SCI 分区 | Q1 |
| IF | 5.7 |
| 研究类型 | 综述 Meta · 基础／转化 |
| 所属专科 | 鼻科 |
中文摘要
环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子（cGAS-STING）信号通路经典上被认为是固有抗病毒免疫中关键的胞质DNA感知机制，如今正逐渐显现为无菌性炎症和免疫失调的关键调节因子。近期证据已转变了范式，揭示其显著参与多种过敏性疾病的发病机制，包括哮喘、特应性皮炎和过敏性鼻炎。除了其在感染中的经典作用外，来自线粒体应激、细胞损伤或中性粒细胞胞外诱捕网（NETs）的内源性DNA异常激活cGAS，可驱动促炎细胞因子反应，并根据情境驱动I型干扰素反应；然而，在哮喘气道上皮中，刺激诱导的I型干扰素产生受损，并进一步被2型炎症介质抑制。本综述综合了当前关于失调的cGAS-STING信号如何通过放大Th2反应、促进气道重塑、增强上皮屏障功能障碍以及调节嗜酸性粒细胞、巨噬细胞、肥大细胞、树突状细胞和成纤维细胞等关键免疫细胞活性来促进过敏性炎症的研究发现。我们进一步探讨了该通路与其他过敏信号级联之间的相互作用，强调其作为过敏性致敏和慢性化的固有免疫放大器的角色。最后，我们讨论了靶向cGAS-STING轴作为管理严重、类固醇抵抗或2型低过敏性内型的新兴治疗策略的转化潜力，同时强调需要进一步验证，特别是在I型干扰素反应受损以及2型低内型直接证据仍然有限的情况下。理解cGAS-STING的新兴作用为过敏性疾病的复杂免疫生物学提供了关键见解，并开辟了新的干预途径。
英文摘要
The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, classically recognized as a crucial cytosolic DNA-sensing mechanism in innate antiviral immunity, is now emerging as a pivotal regulator of sterile inflammation and immune dysregulation. Recent evidence has shifted the paradigm, revealing its significant involvement in the pathogenesis of various allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis. Beyond its canonical role in infection, aberrant activation of cGAS by endogenous DNA from mitochondrial stress, cellular damage, or neutrophil extracellular traps (NETs) can drive pro-inflammatory cytokine responses and, depending on context, type I interferon responses; however, stimulus-induced type I interferon production is impaired in asthmatic airway epithelium and is further suppressed by type 2 inflammatory mediators. This review synthesizes current findings on how dysregulated cGAS-STING signaling contributes to allergic inflammation by amplifying Th2 responses, promoting airway remodeling, enhancing epithelial barrier dysfunction, and modulating the activity of key immune cells such as eosinophils, macrophages, mast cells, dendritic cells, and fibroblasts. We further explore the interplay between this pathway and other allergic signaling cascades, highlighting its role as an innate immune amplifier of allergic sensitization and chronicity Finally, we discuss the translational potential of targeting the cGAS-STING axis as an emerging therapeutic strategy for managing severe, steroid-resistant, or type-2-low allergic endotypes, while emphasizing the need for further validation, particularly in settings where type I interferon responses are impaired and where direct evidence for type-2-low endotypes remains limited.Understanding the emerging role of cGAS-STING provides critical insights into the complex immunobiology of allergic diseases and opens new avenues for intervention.