IFN-ζ/limitin:: a member of type I IFN with mild lympho-myelosuppression

Interferon (IFN)-zeta/limitin has been considered as a novel type I IFN by the Nomenclature Committee of the International Society for Interferon and Cytokine Research. IFN-zeta/limitin shows some sequence homology with IFN-alpha and IFN-beta, has a globular structure with five alpha-helices and four loops, and recognizes IFN-alpha/beta receptor. Although IFN-zeta/limitin displays antiviral, immunomodulatory, and antitumor effects, it has much less lympho-myelosuppressive activities than IFN-alpha. Treatment of cells with type I IFNs induces and/or activates a number of molecules, which regulate cell cycle and apoptosis. It is noteworthy that IFN-zeta/limitin activates the Tyk2-Daxx and Tyk2-Crk pathways weaker than IFN-a. Because experiments using antisense oligonucleotides have revealed their essential role in type I IFN-related suppression of lympho-hematopoiesis, little ability of IFN/limitin to activate the Tyk2-dependent signaling pathway may explain its uniquely narrow range of biological activities. Further analysis of structure-function relationship of type I IFNs will establish an engineered cytokine with useful features of IFN-zeta/Iimitin.