RNA sensing at the crossroads of autoimmunity and autoinflammation

Abstract

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.