Our body expresses sensors to detect pathogens through the recognition of expressed molecules, including nucleic acids, lipids, and proteins, while immune tolerance prevents an overreaction with self and the development of autoimmune disease. Adenosine (A)-to-inosine (I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a post-transcriptional modification that can potentially occur at over 100 million sites in the human genome, mainly in Alu repetitive elements that preferentially form a double-stranded RNA (dsRNA) structure. A-to-I conversion within dsRNA, which may induce a structural change, is required to escape from the host immune system, given that endogenous dsRNAs transcribed from Alu repetitive elements are potentially recognized by melanoma differentiation-associated protein 5 (MDA5) as non-self. Of note, loss-of-function mutations in the ADAR1 gene cause Aicardi–Goutières syndrome, a congenital autoimmune disease characterized by encephalopathy and a type I interferon (IFN) signature. However, the loss of ADAR1 in cancer cells with an IFN signature induces lethality via the activation of protein kinase R in addition to MDA5. This makes cells more sensitive to immunotherapy, highlighting the opposing immune status of autoimmune diseases (overreaction) and cancer (tolerance). In this review, we provide an overview of insights into two opposing aspects of RNA editing that functions as a modulator of the immune system in autoimmune diseases and cancer.

我们的身体会表达传感器，通过识别表达的分子来检测病原体，包括核酸，脂质和蛋白质，而免疫耐受则可防止自身过度反应和自身免疫性疾病的发展。腺苷（A）到肌苷（I）的RNA编辑，是由作用于RNA（ADARs）的腺苷脱氨酶催化的，是一种转录后修饰，可能发生在人类基因组的1亿多个位点上，主要是在Alu重复元件中优先形成双链RNA（dsRNA）结构。鉴于可能从Alu转录出内源性dsRNA，dsRNA内的A到I转换可能会导致结构改变，这需要从宿主免疫系统逃脱。黑色素瘤分化相关蛋白5（MDA5）可能将重复元件识别为非自身。值得注意的是，ADAR1基因的功能丧失突变会导致Aicardi–Goutières综合征，这是一种以脑病和I型干扰素（IFN）为特征的先天性自身免疫疾病。然而，癌细胞中具有IFN标记的ADAR1的丢失会通过除MDA5之外的蛋白激酶R的激活而导致致死性。这使细胞对免疫疗法更加敏感，突出了自身免疫性疾病（过度反应）和癌症（耐受性）的相反免疫状态。在这篇综述中，我们提供了对RNA编辑的两个相反方面的见解的概述，RNA编辑在自身免疫性疾病和癌症中充当免疫系统的调节剂。