Nuclear factor kappa-light-chain-enhancer of activated B cells and Type I interferon signaling pathways (NF-κB/Type I IFN pathways)

The NF-κB and Type I interferon-linked inflammatory signaling pathways constitute a fundamental regulatory network governing the host's innate and adaptive immune responses (UniProt P19838, P01574). NF-κB is a family of inducible transcription factors that trigger the production of pro-inflammatory cytokines and cell survival signals, while Type I interferons (IFN-α/β) are critical for establishing an antiviral state and modulating immune cell maturation (Ivashkiv & Donlin, Nature Reviews Immunology, 2014). These pathways are often co-activated by pattern recognition receptors (PRRs) like TLRs and cGAS-STING, which detect pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Dysregulation of this crosstalk—characterized by persistent NF-κB activation and an elevated 'interferon signature'—is a central driver in the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis, as well as various cancers and autoinflammatory 'interferonopathies' (PubMed: 24445666). Pharmacological targeting of this network is a cornerstone of modern therapy, utilizing JAK inhibitors to block IFN signaling and proteasome inhibitors or corticosteroids to suppress NF-κB activity (StatPearls: NF-KappaB Pathway).

Other names

NF-kappaB and Type I IFN signalingPro-inflammatory and antiviral signaling networkNFKB-IFN axiscGAS-STING-IFN-NFKB axisInnate immune signaling pathways

Therapeutic modulation of these pathways involves inhibiting signal transduction at multiple nodes: blocking Type I interferon receptors (e.g., IFNAR1), inhibiting Janus kinases (JAK1/2/3) to prevent STAT phosphorylation, inhibiting the IKK complex to prevent NF-κB activation, or using proteasome inhibitors to prevent the degradation of IκB, thereby sequestering NF-κB in the cytoplasm.