Innate RNA-sensing receptors (RSRs)

Innate RNA-sensing receptors are a specialized group of pattern recognition receptors (PRRs) expressed in dendritic cells and other immune cells to detect foreign or mislocalized RNA (Schlee & Hartmann, 2016, Nature Reviews Immunology). These receptors are broadly divided into endosomal Toll-like receptors (TLR3, TLR7, and TLR8) and cytosolic RIG-I-like receptors, such as RIG-I (DDX58) and MDA5 (IFIH1) (Rehwinkel & Gack, 2020, Nature Reviews Immunology). Upon activation by viral or endogenous RNA ligands, they initiate signaling pathways through adapters such as MyD88, TRIF, or MAVS, ultimately triggering the expression of type I interferons and pro-inflammatory cytokines (Kawai & Akira, 2011, Nature Immunology). These pathways are critical for mounting an effective antiviral response and bridging innate and adaptive immunity. In clinical practice, agonists of these receptors, such as Imiquimod or Poly(I:C) derivatives, are utilized as vaccine adjuvants and in cancer immunotherapy to enhance immune surveillance (Worah et al., 2019, Frontiers in Immunology). Conversely, antagonists are under investigation for treating autoimmune conditions like systemic lupus erythematosus, where RNA sensing is pathologically overactive. The therapeutic challenge lies in balancing the induction of a robust immune response with the risk of systemic toxicity or the development of chronic inflammation.

Other names

RNA pattern recognition receptorsEndosomal RNA sensorsCytosolic RNA sensorsRNA-sensing PRRsToll-like receptors 3/7/8RIG-I-like receptors

Agonism of endosomal or cytosolic receptors to induce pro-inflammatory cytokines and type I interferons for antiviral or antitumor activity; Antagonism to suppress inappropriate immune activation in autoimmune diseases.