title: The molecular basis for functional plasticity in type I interferon signaling.
abstract: Type I interferons (IFNs) are best known for their role in innate immunity, but they are also involved in other functions including immunomodulation, restricting proliferation, cancer surveillance, and the regulation of the adaptive immune response. All these responses are mediated through the interaction with a single cell surface receptor, albeit at different ligand and receptor concentrations, ligand subtypes, and time of activation. Here we review the functional plasticity of IFN signaling from a quantitative perspective, showing how variations in different ingredients of the system lead to differential IFN responses and how cells tune the system to maximize efficiency while minimizing detrimental effects. We present a basic model wherein the integrated action of different feedback mechanisms can provide sufficient temporal control to differentially drive cellular decisions.
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: gideon.schreiber@weizmann.ac.il.
authors: Gideon
authors: G
authors: Schreiber
authors: Department of Biology, University of Osnabrück, 49076 Osnabrück, Germany. Electronic address: jacob.piehler@biologie.uni-osnabrueck.de.
authors: Jacob
authors: J
authors: Piehler
mesh_terms: D056704:Adaptive Immunity; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007157:Immunologic Surveillance; D056747:Immunomodulation; D007370:Interferon Type I / Q000145:classification / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000145:classification / Q000235:genetics / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D007370:Interferon Type I; D007378:Interleukins; D018121:Receptors, Cytokine; D053633:Receptor, Interferon alpha-beta