Interferons (IFNs) are a family of mammalian cytokines initially characterized by their ability to inhibit viral infection. In addition to their antiviral properties, IFNs have also been shown to exhibit antiproliferative, immunomodulatory, and neuroinflammatory activities.
In humans, IFN-alpha consists of a group of proteins that are greater than 85% homologous by amino acid sequence. Encoded by a gene cluster on chromosome 9, there exist 12 distinct human IFN-alpha subtypes that include IFN-α1, IFN-α2, IFN-α4, IFN-α5, IFN-α6, IFN-α7, IFN-α8, IFN-α10, IFN-α14, IFN-α16, IFN-α17, and IFN-α21. Despite their structural similarities, these subtypes have long been understood to have differing activities in a variety of assay systems. These variations contribute to the diverse responses initiated by the immune system to combat pathogens and regulate immune processes effectively.
All IFN-alpha subtypes signal through the IFN-alpha/beta Receptor complex that is composed of two subunits, IFNAR1 and IFNAR2. Binding to this receptor complex varies differently among the IFN-alpha subtypes and contributes to the diverse immune responses. The table below summarizes some of the biological features of the subtypes as well as their binding affinities to the IFNAR1 and IFNAR2 receptor subunits.
With the yin-yang role that IFN-alpha may play in different diseases, understanding their subtype-specific functions, receptor interactions, and clinical applications is essential for advancing therapeutic strategies.
