Type I and type II interferon pathways (IFN pathways)

The Type I and Type II interferon pathways are critical components of the innate and adaptive immune systems, primarily responsible for antiviral defense and immune regulation [13, 18]. Type I interferons (e.g., IFN-alpha, IFN-beta) signal through the IFNAR receptor complex to activate the JAK1/TYK2 kinases and the ISGF3 transcription factor complex, inducing an antiviral state in cells [12, 17]. Type II interferon (IFN-gamma) signals through the IFNGR complex, activating JAK1/JAK2 and STAT1 homodimers to promote pro-inflammatory responses and MHC expression [4, 19]. Dysregulation of these pathways is linked to various pathologies, including systemic lupus erythematosus (characterized by a 'Type I IFN signature') and viral susceptibility [2, 15]. Therapeutic interventions include recombinant interferons for multiple sclerosis and hepatitis, as well as JAK inhibitors and monoclonal antibodies like anifrolumab to dampen overactive signaling in autoimmune conditions [1, 8, 11].

Other names

Interferon signalingIFN-alpha/beta and IFN-gamma pathwaysJAK-STAT interferon signaling

Drugs modulate these pathways by either mimicking the endogenous ligands (recombinant interferon therapies), blocking the receptor subunits (e.g., anifrolumab targeting IFNAR1), or inhibiting the downstream intracellular kinases (JAK1, JAK2, or TYK2 inhibitors) to alter the transcription of interferon-stimulated genes (ISGs) [1, 4, 12, 25].