New aspects of IFN‐α/β signalling in immunity, oncogenesis and bone metabolism

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Abstract
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‐α/β 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‐α/β system. A weak signal by constitutively produced IFN‐α/β is critical not only for the regulation of cellular amplification of IFN‐α/β 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‐β signalling is critical for the regulation of the bone‐resorbing osteo‐clasts. In this review, we focus on the newly discovered roles of the IFN‐α/β system in host defense and bone remodeling, particularly on the functions of the weak IFN‐α/β signalling in the context of what we refer to as the “rewing‐up” model. (Cancer Sci 2003; 94: 405–411)