Interferons as key factors for pathogenesis, diagnostics and treatment New knowledge on inflammatory diseases in childhood

Interferons (IFN) belong to a family of related signalling proteins that are classified into the three major types IFN-alpha, IFN-beta (together type 1 IFN), and IFN-gamma (single type 2 IFN). Binding to specific receptors results in activation of a signal transduction pathway though which the expression of a wide range of genes is activated. The specific functions of the various IFNs are markedly complex. Depending on the context, IFNs are essential for physiological host-defense mechanisms, but can also have a pathophysiological relevance in various inflammatory diseases involving both autoimmunity and hyperinflammation. The importance of IFNs in the pathogenesis of chronic inflammatory diseases is particularly evident in their contribution to hereditary diseases with constitutive type 1 IFN activity (so-called interferonopathies). New evidence demonstrates the importance of type 2 IFN in hyperinflammation and cytokine storm syndromes. This article reviews the most prominent features of the interferon system, with a focus on recent clinically relevant discoveries on monitoring IFN activity and related therapeutic perspectives.