Interferon-kappa, a novel type I interferon expressed in human keratinocytes

High throughput cDNA sequencing has led to the identification of interferon -kappa, a novel subclass of type I interferon that displays similar to 30% homology to other family members. Interferon-kappa consists of 207 amino ac ids, including a 27-amino acid signal peptide and a series of cysteines con served in type I interferons. The gene encoding interferon-kappa is located on the short arm of chromosome 9 adjacent to the type I interferon gene cl uster and is selectively expressed in epidermal keratinocytes. Expression o f interferon-kappa is significantly enhanced in keratinocytes upon viral in fection, upon exposure to double-stranded RNA, or upon treatment with eithe r interferon-gamma or interferon-beta. Administration of interferon-kappa r ecombinant protein imparts cellular protection against viral infection in a species-specific manner. Interferon-kappa activates the interferon-stimula ted response element signaling pathway and a panel of genes similar to thos e regulated by other type I interferons including anti-viral mediators and transcriptional regulators. An antibody that neutralizes the type I interfe ron receptor completely blocks interferon-kappa signaling, demonstrating th at interferon-kappa utilizes the same receptor as other type I interferons. Interferon-kappa therefore defines a novel subclass of type I interferon t hat is expressed in keratinocytes and expands the repertoire of known prote ins mediating host defense.