Williams Sandra G, Sim Soyeong, Wolin Sandra L
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA
RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.
RNA. 2025 Feb 19;31(3):369-381. doi: 10.1261/rna.080304.124.
Immune-mediated diseases are common in humans. The immune system is a complex host defense system that evolved to protect us from pathogens, but also plays an important role in homeostatic processes, removing dead or senescent cells, and participating in tumor surveillance. The human immune system has two arms: the older innate immune system and the newer adaptive immune system. Sensing of foreign RNA is critical to the innate immune system's ability to recognize pathogens, especially viral infections. However, RNA sensors are also strongly implicated in autoimmune and autoinflammatory diseases, highlighting the importance of balancing pathogen recognition with tolerance to host RNAs that can resemble their viral counterparts. We describe how RNA sensors bind their ligands, how this binding is coupled to upregulation of type I interferon-stimulated genes, and the ways in which mutations in RNA sensors and genes that play important roles in RNA homeostasis have been linked to autoimmune and autoinflammatory diseases.
免疫介导的疾病在人类中很常见。免疫系统是一个复杂的宿主防御系统，其进化目的是保护我们免受病原体侵害，但在稳态过程、清除死亡或衰老细胞以及参与肿瘤监测中也发挥着重要作用。人类免疫系统有两个分支：较古老的固有免疫系统和较新的适应性免疫系统。对外源RNA的感知对于固有免疫系统识别病原体的能力至关重要，尤其是在病毒感染方面。然而，RNA传感器也与自身免疫性疾病和自身炎症性疾病密切相关，这凸显了在识别病原体与耐受可能类似于病毒对应物的宿主RNA之间保持平衡的重要性。我们描述了RNA传感器如何结合其配体，这种结合如何与I型干扰素刺激基因的上调相关联，以及RNA传感器和在RNA稳态中起重要作用的基因中的突变与自身免疫性疾病和自身炎症性疾病相关联的方式。
