Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, United States; Institute of High-Tech Biomedicine, Petrozavodsk State University, 33 Lenin str., Petrozavodsk 185910, Russian Federation.
Institute of High-Tech Biomedicine, Petrozavodsk State University, 33 Lenin str., Petrozavodsk 185910, Russian Federation.
Cytokine Growth Factor Rev. 2016 Jun;29:83-91. doi: 10.1016/j.cytogfr.2016.02.009. Epub 2016 Mar 4.
Thanks to the numerous studies that have been carried out recently in the field of cytosolic DNA sensing, STING (Stimulator of Interferon Genes) is now recognized as a key mediator of innate immune signaling. A substantial body of evidence derived from in vivo mouse models demonstrates that STING-regulated pathways underlie the pathogenesis of many diseases including infectious diseases and cancers. It has also become evident from these studies that STING is a promising therapeutic target for the treatment of cancer. However, mouse strains commonly used for modelling innate immune response against infections or tumors do not allow investigators to accurately reproduce certain specific characteristics of immune response observed in human cells. In this review, we will discuss recent data demonstrating that the use of wild-derived genetically distinct inbred mice as a model for investigation into the innate immunity signaling networks may provide valuable insight into the STING-regulated pathways specific for human cells. The maximum complexity of STING-mediated mechanisms can probably be seen in case of DNA virus-induced carcinogenesis in which STING may perform unexpected biological activities. Therefore, in another part of this review we will summarize emerging data on the role of STING in human DNA virus-related oncopathologies, with particular attention to HPV-associated cervical cancer, aiming to demonstrate that STING indeed "starts a new chapter" in research on this issue and that wild-derived mouse models of STING-mediated response to infections will probably be helpful in finding out molecular basis for clinical observations.
由于最近在细胞质 DNA 感应领域进行了大量研究，STING（干扰素基因刺激物）现在被认为是先天免疫信号转导的关键介质。大量来自体内小鼠模型的证据表明，STING 调节的途径是许多疾病（包括传染病和癌症）发病机制的基础。这些研究还表明，STING 是治疗癌症的有前途的治疗靶点。然而，通常用于模拟感染或肿瘤的先天免疫反应的小鼠品系不能使研究人员准确再现人类细胞中观察到的某些特定免疫反应特征。在这篇综述中，我们将讨论最近的数据，这些数据表明，使用野生来源的遗传上不同的近交系小鼠作为研究先天免疫信号网络的模型，可能为研究人类细胞特有的 STING 调节途径提供有价值的见解。在 DNA 病毒诱导的致癌作用中，可能会看到 STING 介导的机制的最大复杂性，因为在这种情况下，STING 可能会表现出意想不到的生物学活性。因此，在这篇综述的另一部分，我们将总结 STING 在人类 DNA 病毒相关致癌病理中的作用的新数据，特别关注 HPV 相关的宫颈癌，旨在证明 STING 确实在这个问题的研究中“开启了新篇章”，并且对感染的 STING 介导反应的野生来源小鼠模型可能有助于发现临床观察的分子基础。
