New aspects of IFN-alpha/beta signalling in immunity, oncogenesis and bone metabolism.

Although interferons (IFNs) were originally identified as humoral factors that confer an antiviral state upon cells, they have been demonstrated to be multifunctional in a variety of biological systems. The IFN-alpha/beta system modulates not only the cellular immune response to viral and bacterial infections, but also the oncogenic process and bone metabolism. Further studies have revealed additional unique facets of the IFN-alpha/beta system. A weak signal by constitutively produced IFN-alpha/beta is critical not only for the regulation of cellular amplification of IFN-alpha/beta production upon viral infection or the enhancement of signalling by other cytokines, but also for the regulation of adaptive immune responses, such as the enhancement of CD8()+ T cell activation. Furthermore, IFN-beta signalling is critical for the regulation of the bone-resorbing osteoclasts. In this review, we focus on the newly discovered roles of the IFN-alpha/beta system in host defense and bone remodeling, particularly on the functions of the weak IFN-alpha/beta signalling in the context of what we refer to as the "revving-up" model.