Fig. 4

A schematic presentation regarding the mechanisms of action of glucocorticoids. In normal conditions, IFN β binding to its receptor triggers the formation of the ISG3 complex consisting of Stat1, Stat2, and IRF9. This complex then trans-locates from the cytoplasm to the nucleus where it binds to the interferon-stimulated response element (ISRE) in hundreds of interferon-stimulated genes (ISG) leading to the production of interferon-stimulated proteins. Glucocorticoids have at least two different forms of action in this setting. (1) Glucocorticoids prevent the formation of the ISG3 complex and thus prevent activation of the IFN-beta responsive genes. (2) Glucocorticoids bind to its receptor (GR) and this complex moves from the cytoplasm to the nucleus and binds to the glucocorticoid binding site of the IFNAR2 gene, if the individual has TT at SNP rs9984273. This seems to lead to repression seen as low expression of IFNAR2. In contrast, if the individual has CC or CT this binding does not efficiently take place resulting in higher expression of IFNAR2 than in TT individuals. The size and intensity of the glucocorticoid/GR complex and the IFNAR2 gene illustrate the relative magnitude of the phenomenon in CT vs TT patients