Class II cytokine receptors and their ligands: Key antiviral and inflammatory modulators

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Abstract
Type II cytokine receptors consist of 1 soluble and 11 transmembrane proteins that have 20–30% amino-acid identity in their extracellular domain. The ligands have a common structure with six α-helices, organized as monomers or homodimers, and have 20–30% amino-acid identity. Receptors associate as heterodimers including common chains and a high level of complexity in cytokine–receptor interactions results from the fact that one particular cytokine can bind to two different receptor complexes, and that one particular receptor complex can bind several cytokines. Type I interferons (IFNs), IL-28 and IL-29 have important roles in antiviral responses through the activation of signal transducer and activator of transcription 2 (STAT2). Inflammatory responses are modulated by members of this family; IL-10 and IFN-γ have anti- and pro-inflammatory activities, respectively; IL-22 induces the production of acute-phase reactants and IL-20 regulates the proliferation of keratinocytes. Antitumour activities have been described for type I IFNs and IL-24 delivered by adenoviruses through an unknown mechanism, potentially independent from IL-24 receptor activation.