Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom; email:
Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Paris 75015, France.
Annu Rev Immunol. 2019 Apr 26;37:247-267. doi: 10.1146/annurev-immunol-042718-041257. Epub 2019 Jan 11.
Recognition of foreign nucleic acids is the primary mechanism by which a type I interferon-mediated antiviral response is triggered. Given that human cells are replete with DNA and RNA, this evolutionary strategy poses an inherent biological challenge, i.e., the fundamental requirement to reliably differentiate self-nucleic acids from nonself nucleic acids. We suggest that the group of Mendelian inborn errors of immunity referred to as the type I interferonopathies relate to a breakdown of self/nonself discrimination, with the associated mutant genotypes involving molecules playing direct or indirect roles in nucleic acid signaling. This perspective begs the question as to the sources of self-derived nucleic acids that drive an inappropriate immune response. Resolving this question will provide fundamental insights into immune tolerance, antiviral signaling, and complex autoinflammatory disease states. Here we develop these ideas, discussing type I interferonopathies within the broader framework of nucleic acid-driven inflammation.
识别外来核酸是触发 I 型干扰素介导的抗病毒反应的主要机制。鉴于人体细胞富含 DNA 和 RNA，这种进化策略带来了一个内在的生物学挑战，即必须可靠地区分自身核酸和非自身核酸。我们认为，一类被称为 I 型干扰素病的孟德尔遗传性免疫缺陷与自身/非自身识别的破坏有关，相关的突变基因型涉及在核酸信号中起直接或间接作用的分子。这种观点提出了一个问题，即哪些自身来源的核酸会引发不适当的免疫反应。解决这个问题将为免疫耐受、抗病毒信号和复杂的自身炎症性疾病状态提供基础的见解。在这里，我们在核酸驱动的炎症的更广泛框架内发展这些想法，讨论 I 型干扰素病。
