Innate immune RNA sensors and type I interferon receptor (RNA-IFNAR axis)

The Innate immune RNA sensors and type I interferon receptor axis represents a critical pathway for detecting viral pathogens and initiating protective immune responses. RNA sensors, including RIG-I-like receptors (RIG-I, MDA5) and Toll-like receptors (TLR3, TLR7, TLR8), recognize foreign or mislocalized RNA, leading to the production of Type I Interferons (IFN-α/β) (Source: UniProt O95786, Q9BYX4). These interferons signal through the Type I Interferon Receptor (IFNAR), a heterodimer of IFNAR1 and IFNAR2, to activate the JAK-STAT pathway and induce interferon-stimulated genes (ISGs) (Source: UniProt P17181, P48551). Overactivation of this pathway is a hallmark of autoimmune interferonopathies such as Systemic Lupus Erythematosus (SLE), while its targeted activation is explored in cancer immunotherapy to enhance T-cell responses (Source: PubMed PMID: 30635665). Therapeutic agents like anifrolumab target IFNAR1 to treat SLE, whereas agonists of RNA sensors like TLR7/8 are used as vaccine adjuvants or in oncology (Source: FDA, PubChem). Balancing this pathway is clinically challenging due to the risk of cytokine storms upon over-activation or increased viral susceptibility upon inhibition.

Other names

RNA-sensing pathwayType I interferon signaling pathwayPRR-IFN axisInnate immune RNA-sensing and IFNAR signaling

Agonism of RNA sensors (TLRs, RLRs) to induce interferon production for antiviral/antitumor effects, or antagonism of IFNAR to block downstream signaling in autoimmune diseases.