IFN-α/β receptor interactions to biologic outcomes:: Understanding the circuitry

Type I interferons (IFNs), which include the IFN-alphas, IFN-beta, IFN-omega, IFN-kappa, and IFN-tau, are an evolutionarily conserved group of secreted cytokines that serve as potent extracellular mediators of host defense and homeostasis. Binding of IFNs to specific cell surface receptors results in the activation of multiple intracellular signaling cascades, leading to the synthesis of proteins that mediate antiviral, growth inhibitory and immunomodulatory responses. In the past decade, considerable information has accumulated pertaining to the different signaling pathways that are activated by the type I IFNs. Although many of the literature findings are specific to defined cell systems or are tissue restricted, the intent of this review is to place these signaling cascades and their effectors in the context of distinct biologic outcomes.