Innate immune nucleic acid-sensing receptor (NASR) (NASR)

Innate immune nucleic acid-sensing receptors represent a broad class of pattern recognition receptors (PRRs) that detect exogenous or misplaced endogenous DNA and RNA to trigger defensive immune responses (PubMed: 30635957). These sensors are strategically localized in endosomes (e.g., TLR3, TLR7, TLR8, TLR9) and the cytoplasm (e.g., cGAS, RIG-I, MDA5, AIM2) to monitor for viral and bacterial invasion or cellular damage (PubMed: 24332878). Upon ligand binding, these receptors activate signaling pathways involving adaptor proteins like STING, MAVS, or MyD88, ultimately leading to the induction of type I interferons and pro-inflammatory cytokines via IRF and NF-κB transcription factors (PubMed: 31142854). In the context of oncology, pharmacological activation of these pathways is a major strategy to enhance tumor immunogenicity and overcome resistance to checkpoint inhibitors (PubMed: 32661320). Conversely, aberrant sensing of self-nucleic acids is a hallmark of various autoimmune and autoinflammatory conditions, making these receptors and their downstream effectors attractive targets for inhibitory therapeutic intervention (PubMed: 25680284).

Other names

Nucleic acid sensorPattern recognition receptorPRRCytosolic DNA sensorRNA sensorEndosomal Toll-like receptor

Agonism of endosomal or cytosolic sensors to induce type I interferon and pro-inflammatory cytokine production for antiviral or antitumor activity; Antagonism to prevent recognition of self-nucleic acids in autoimmune disorders (PubMed: 31142854).