Retinoic acid-inducible gene I-like receptor (RLR)

Retinoic acid-inducible gene I-like receptors are a family of cytosolic pattern recognition receptors that play a frontline role in human innate immunity by sensing specific motifs of viral RNA in the cell cytoplasm. The canonical members are RIG-I, MDA5, and LGP2, each with distinct ligand specificity (RIG-I for short 5’-triphosphate dsRNA, MDA5 for long dsRNA, LGP2 as a regulator). Upon binding viral RNA, these receptors activate signaling through the adaptor MAVS, leading to the transcriptional induction of type I interferons and other antiviral and proinflammatory genes. RLR activation is critical for host defense against a broad spectrum of RNA viruses, and their dysregulation is implicated in cancer (as therapeutic targets and biomarkers), autoimmunity, autoinflammation, and some infections. RLR agonists are under development and investigation for antiviral, anti-tumor, and immunomodulatory therapies, but safety concerns regarding immune overactivation remain.

Other names

RIG-I-like receptorRetinoic acid-inducible gene I-like receptor (RLR)RIG-I (for individual family member)MDA5 (Melanoma differentiation-associated protein 5)LGP2 (Laboratory of genetics and physiology 2)DExD/H box RNA helicases (structural/functional description)

Activation of type I interferon production via RLR signaling; Induction of proinflammatory cytokines; Promotion of immunogenic cell death and anti-tumor immunity; Stimulating apoptosis in infected or malignant cells; Enhancement of immune checkpoint therapy (combination with immune adjuvants)