Nuclear innate sensors for nucleic acids in immunity and inflammation

Abstract Innate sensors recognize pathogen‐associated molecular patterns (PAMPs) or damage‐associated molecular patterns (DAMPs) to initiate innate immune response by activating downstream signaling. These evolutionarily conserved innate sensors usually locate in the plasma membrane or cytoplasm. However, the nucleus‐localized innate sensors are recently found to detect pathogenic nucleic acids for initiating innate response, demonstrating a complicated crosstalk with cytoplasmic sensors and signaling molecules to form an elaborate tiered innate signaling network between nucleus and cytoplasm. Furthermore, these nuclear innate sensors evolve varied mechanisms for discriminating self from non‐self nucleic acids to maintain immune homeostasis and avoid autoinflammatory immune response. In this review, we summarize the recent findings on the identification of nuclear innate sensors for nucleic acids, such as hnRNPA2B1, IFI16, SAFA, and their roles in host defense and inflammatory response.