Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece.
Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Pharmacol Ther. 2015 Oct;154:36-56. doi: 10.1016/j.pharmthera.2015.06.011. Epub 2015 Jul 3.
The characteristic feature of healthy living organisms is the preservation of homeostasis. Compelling evidence highlight that the DNA damage response and repair (DDR/R) and immune response (ImmR) signaling networks work together favoring the harmonized function of (multi)cellular organisms. DNA and RNA viruses activate the DDR/R machinery in the host cells both directly and indirectly. Activation of DDR/R in turn favors the immunogenicity of the incipient cell. Hence, stimulation of DDR/R by exogenous or endogenous insults triggers innate and adaptive ImmR. The immunogenic properties of ionizing radiation, a prototypic DDR/R inducer, serve as suitable examples of how DDR/R stimulation alerts host immunity. Thus, critical cellular danger signals stimulate defense at the systemic level and vice versa. Disruption of DDR/R-ImmR cross talk compromises (multi)cellular integrity, leading to cell-cycle-related and immune defects. The emerging DDR/R-ImmR concept opens up a new avenue of therapeutic options, recalling the Hippocrates quote "everything in excess is opposed by nature."
健康生物的特征是保持内稳态。有力的证据强调，DNA 损伤反应和修复 (DDR/R) 和免疫反应 (ImmR) 信号网络共同作用，有利于多细胞生物的协调功能。DNA 和 RNA 病毒直接和间接地激活宿主细胞中的 DDR/R 机制。DDR/R 的激活反过来又有利于初始细胞的免疫原性。因此，外源性或内源性损伤刺激 DDR/R 会引发先天和适应性 ImmR。电离辐射是 DDR/R 诱导剂的典型代表，其免疫原性为 DDR/R 刺激如何提醒宿主免疫提供了恰当的例子。因此，关键的细胞危险信号在系统水平上刺激防御，反之亦然。DDR/R-ImmR 串扰的破坏会损害（多）细胞的完整性，导致与细胞周期相关的和免疫缺陷。新兴的 DDR/R-ImmR 概念为治疗选择开辟了新途径，这让人想起了希波克拉底的名言“万物过犹不及”。
