Interferon synthesis pathways (IFN synthesis pathways)

Interferon synthesis pathways comprise the intracellular signaling cascades responsible for the production of Type I, II, and III interferons in response to cellular stress or pathogen detection (Ivashkiv & Donlin, 2014). These pathways are initiated by pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and the cGAS-STING system, which sense foreign nucleic acids or proteins (Kawai & Akira, 2010). Upon activation, these receptors trigger a series of phosphorylation events involving kinases such as TBK1 and IKKε, ultimately leading to the activation of interferon regulatory factors (IRFs) like IRF3 and IRF7 (Ablasser & Chen, 2019). These transcription factors translocate to the nucleus to drive the expression of interferon genes, which are critical for establishing an antiviral state and modulating the adaptive immune response. Dysregulation of these pathways is central to the pathogenesis of various conditions, including viral infections, where insufficient production allows viral escape, and autoimmune interferonopathies, where chronic overproduction leads to systemic inflammation (Crow & Manel, 2015). In oncology, pharmacological activation of these pathways, particularly via STING or TLR agonists, is being explored to turn cold tumors hot by enhancing dendritic cell activation and T-cell recruitment. Conversely, inhibitors of these pathways are under investigation for treating systemic lupus erythematosus and other autoinflammatory disorders.

Other names

Type I interferon inductionIFN production pathwayInnate antiviral signalingInterferon induction cascade

Pharmacological modulation of pattern recognition receptors (PRRs) or downstream signaling kinases to regulate the transcriptional induction of interferon genes.