Type I interferons (IFN-α/β)

Type I interferons — primarily IFN-α (multiple subtypes) and IFN-β — are cytokines secreted by virtually all nucleated cells in response to viral nucleic acids detected by innate pattern recognition receptors, most prominently the cGAS-STING pathway for cytosolic DNA, and TLR7/TLR9 for endosomal RNA/DNA. They signal through the IFNAR1/IFNAR2 receptor complex to induce hundreds of interferon-stimulated genes that establish an antiviral cellular state, activate NK cells, and bridge innate to adaptive immunity. Chronic, low-level type I IFN signalling — driven in aging by accumulated cytosolic DNA fragments, mitochondrial DNA leakage, and retrotransposon activity that activates cGAS-STING — is an important contributor to inflammaging. Pathological extremes of constitutive type I IFN activation are exemplified by SAVI (STING-associated vasculopathy with onset in infancy) and Singleton-Merten syndrome, monogenic interferonopathies that illustrate the tissue-damaging potential of uncontrolled type I IFN signalling.