Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Nat Rev Immunol. 2019 Mar;19(3):141-153. doi: 10.1038/s41577-018-0117-0.
The immune system detects disturbances in homeostasis that occur during infection, sterile tissue damage and cancer. This initiates immune responses that seek to eliminate the trigger of immune activation and to re-establish homeostasis. At the same time, these mechanisms can also play a crucial role in the progression of disease. The occurrence of DNA in the cytosol constitutes a potent trigger for the innate immune system, governing the production of key inflammatory cytokines such as type I interferons and IL-1β. More recently, it has become clear that cytosolic DNA also triggers other biological responses, including various forms of programmed cell death. In this article, we review the emerging literature on the pathways governing DNA-stimulated cell death and the current knowledge on how these processes shape immune responses to exogenous and endogenous challenges.
免疫系统检测到感染、无菌组织损伤和癌症过程中发生的体内平衡紊乱。这会启动免疫反应，试图消除免疫激活的触发因素并重新建立体内平衡。与此同时，这些机制也可以在疾病的进展中发挥关键作用。细胞质中的 DNA 的存在构成了先天免疫系统的有效触发因素，控制着关键炎症细胞因子（如 I 型干扰素和 IL-1β）的产生。最近，人们清楚地认识到，细胞质 DNA 还会引发其他生物学反应，包括各种形式的程序性细胞死亡。在本文中，我们综述了关于调控 DNA 刺激细胞死亡的途径的新文献，并介绍了这些过程如何影响对外源和内源性挑战的免疫反应的现有知识。
