Interferon-κ, a Novel Type I Interferon Expressed in Human Keratinocytes

High throughput cDNA sequencing has led to the identification of interferon-κ, a novel subclass of type I interferon that displays ∼30% homology to other family members. Interferon-κ consists of 207 amino acids, including a 27-amino acid signal peptide and a series of cysteines conserved in type I interferons. The gene encoding interferon-κ is located on the short arm of chromosome 9 adjacent to the type I interferon gene cluster and is selectively expressed in epidermal keratinocytes. Expression of interferon-κ is significantly enhanced in keratinocytes upon viral infection, upon exposure to double-stranded RNA, or upon treatment with either interferon-γ or interferon-β. Administration of interferon-κ recombinant protein imparts cellular protection against viral infection in a species-specific manner. Interferon-κ activates the interferon-stimulated response element signaling pathway and a panel of genes similar to those regulated by other type I interferons including anti-viral mediators and transcriptional regulators. An antibody that neutralizes the type I interferon receptor completely blocks interferon-κ signaling, demonstrating that interferon-κ utilizes the same receptor as other type I interferons. Interferon-κ therefore defines a novel subclass of type I interferon that is expressed in keratinocytes and expands the repertoire of known proteins mediating host defense.