Type I interferon system and IRF family of transcription factors in host defense regulation

Type I interferons (IFN-α /β) were originally identified as humoral factors, which are secreted in virally infected cells and confer an antiviral state in uninfected cells. Subsequently, their multifunctional roles have also been demonstrated, which include antitumor actions. More recently, the IFN system has been the focus of much attention in the context of the regulation of the innate and adaptive immune systems. Indeed, the IFN genes are induced in antigen-presenting cells (APCs) via the activation of distinct Toll-like receptors (TLRs), and accumulating evidence indicates the importance of TLR-induced IFN-α /β for the induction of both innate and adaptive immune responses. Two members of the interferon regulatory factor (IRF) family of transcription factors, IRF-3 and IRF-7, play mutually nonredundant functions in IFN-α /β gene induction in response to viral infection or TLR stimulation. Another unique facet of the IFNα /β system is that IFN-α /β are produced at low levels in normally growing cells. Although seemingly futile, a weak signal by these IFNs is critical to eliciting from cells strong responses to other stimuli, thereby providing a foundation for an efficient operation of the immune system. In the context of the antitumor action of IFNs, p53 gene transcription is induced by IFN-α /β, accompanied by an increase in p53 protein level for boosting p53 responses in tumor suppression. Furthermore, a new link was discovered between p53 and IFN-α /β in antiviral immunity. In this review, we focus on recent studies on the type I IFN (IFN-α /β) system and IRF-family transcription factors with respect to immunity and oncogenesis.