IFN1

IFN1, commonly referred to as type I interferons, is a family of cytokines central to antiviral defense and immune regulation. The best characterized members in humans are the interferon-α (IFN-α) subtypes and interferon-β (IFN-β). Other type I interferons exist in various species, including IFN-ω and IFN-κ in some mammals. Type I interferons are produced by many cell types, especially plasmacytoid dendritic cells, in response to viral infection or detection of nucleic acids by pattern recognition receptors such as Toll-like receptors and RIG-I-like receptors.

Mechanism of action: Secreted IFN-1 molecules bind to a common receptor, the interferon-α/β receptor (IFNAR), a heterodimer of subunits IFNAR1 and IFNAR2. Receptor engagement activates JAK-STAT signaling, leading to the transcription of interferon-stimulated genes (ISGs). ISGs encode proteins that inhibit viral replication, degrade viral RNA, enhance antigen presentation, and shape the activity of various immune cells.

Functions and clinical relevance: Type I interferons induce an antiviral state in cells and have broad immunomodulatory effects, influencing natural killer cell activity and cytotoxic T cell responses. Clinically, IFN-α has been used to treat certain viral infections and hematologic cancers, and IFN-β is approved for relapsing forms of multiple sclerosis. Their use can be limited by adverse effects such as flu-like symptoms, cytopenias, fatigue, and mood disturbances. Advances in antiviral therapies have reduced reliance on IFN-1 for many indications.

Genetics and evolution: Type I IFNs are conserved across vertebrates, encoded by multigene families organized in clusters, reflecting gene duplication events that generate multiple subtypes with distinct tissue distributions and regulatory patterns.