IFN-κ

Interferon-kappa (IFN-κ, IFNK) is a skin-biased type I interferon encoded by a solitary gene situated within the type I interferon cluster on human chromosome 9. IFN-κ is preferentially expressed by keratinocytes and, at lower levels, by monocytes and dendritic cells; its transcription is induced upon TLR3, TLR4 or RIG-I activation and by UV exposure, but unlike IFN-β it can also display constitutive expression in epidermis. The mature 180-amino-acid protein shares only about 30% sequence identity with IFN-α and IFN-β, and binds IFNAR1/IFNAR2 with lower apparent affinity, eliciting quantitatively and qualitatively distinct patterns of ISG induction. Functionally, IFN-κ establishes intrinsic antiviral resistance of the epidermal barrier against herpes simplex virus and papillomavirus. Paradoxically, keratinocyte-derived IFN-κ is downregulated during cutaneous lupus and in some skin cancers while being upregulated in psoriasis, reflecting both protective and pathological inflammatory roles in epithelial immunobiology.